Supplementary Appendix
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- Αμάλθεια Σπηλιωτόπουλος
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1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Valk PJM, Verhaak RGW, Beijen MA, et al. Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia. N Engl J Med 2004;350:
2 Web publication only 1. Supporting Materials and Methods Figure A: Guidelines how to read the Omniviz Correlation View 2. Supporting results Pearson s correlation coefficient analyses using Omniviz with different probe subsets Figure B: 147 probe sets Figure C: 293 probe sets Figure D: 569 probe sets Figure E: 984 probe sets Figure F: 1692 probe sets Figure G: 2856 probe sets Figure H: 5071 probe sets 3. Supporting results assigned clusters (2856 probe sets) Figures Figure I: Southern blot analyses AML patients with cryptic inv(16) Figure J: Expression of MYH11 as determined by Affymetrix GeneChip analyses in 285 cases of AML and controls Figure K: Snapshot of Correlation View showing the AML-M3 t(15;17) patients Figure L: Expression of ETO as determined by Affymetrix GeneChip analyses in 285 cases of AML and controls Tables Cluster Characteristics SAM genes #1 (EVI1) Table A Table A1 #2 (FLT3 ITD) Table B Table B1 #3 Table C Table C1 #4 (cebpα) Table D Table D1 #5 Table E Table E1 #6 (FLT3 ITD) Table F Table F1 #7 Table G Table G1 #8 Table H Table H1 #9 (inv(16)) Table I Table I1 #10 (EVI1) Table J Table J1 #11 Table K Table K1 #12 (t(15;17)) Table L Table L1 #13 (t(8;21)) Table M Table M1 #14 Table N Table N1 #15 (cebpα) Table O Table O1 #16 (11q23) Table P Table P1 Summary of frequencies and percentages of cytogenetic and molecular abnormalities for each of the assigned clusters (Table Q). 4. PAM genes of prognostically important clusters (#13, #12, #9, #16, #10, #4, #15, #4 and #15, and FLT3 ITD) (Table R)
3 FAB Figure A: Correlation View and FAB classification of the cohort of 285 AML patients (2856 probe sets). Correlation (red) between cluster #5 and #16 is indicated by rectangle. Both clusters predominantly consist of AML-M5 and correlate. However, they do form separate clusters. Anticorrelation (blue) for instance between cluster 5 and cluster #13, which merely contains AML-M2, is indicated by the dashed rectangle. Correlation and anti-correlation between every individual (sub)cluster can be extracted from the Correlation View and (sub)clusters can subsequently be assigned, e.g., cluster #6, #7 and #8 (dotted lines). FAB: M0-bright green, M1-green, M2-pink, M3- orange, M4-purple, M5-turquoise, M6-yellow (with number).
4 Figure B: Pearson s correlation coefficient analyses using Omniviz with 147 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
5 Figure C: Pearson s correlation coefficient analyses using Omniviz with 293 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
6 Figure D: Pearson s correlation coefficient analyses using Omniviz with 569 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
7 Figure E: Pearson s correlation coefficient analyses using Omniviz with 984 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
8 Figure F: Pearson s correlation coefficient analyses using Omniviz with 1692 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
9 Figure G: Pearson s correlation coefficient analyses using Omniviz with 2856 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
10 Figure H: Pearson s correlation coefficient analyses using Omniviz with 5071 probe sets. In the Correlation View all 285 patients are plotted versus all 285 AML patients. FAB classification and karyotype based on cytogenetics are depicted in the columns along the original diagonal of the Correlation View (FAB M0-black, M1-green, M2-purple, M3-orange, M4-yellow, M5-turquoise, M6-grey; karyotype: normal-green, inv(16)-yellow, t(8;21)-purple, t(15;17)-orange, 11q23 abnormalities-turquoise, 7(q) abnormalities-red, +8-pink, complex-black, other-grey). FLT3 ITD, FLT3 TKD, N-RAS, K-RAS and cebpα mutations and EVI1 overexpression are depicted in the same set of columns (red bar: positive and green bar: negative).
11 WT WT inv(16) type A inv(16) type A inv(16) type E BamHI - normal allele EcoRI - normal allele Figure I: Southern blot analyses AML patients with cryptic inv(16). Southern blot analyses was carried out with a myosine heavy chain 11 specific probe (NT , nt) on material of AML (WT, no inv(16)), AML with known inv(16) breakpoint (type A and E) and three patients that clustered with all known AML with inv(16) patients in the Correlation View (Figure 1).
12 MYH11 expression 8,0 7,0 6,0 5,0 4,0 3,0 -inv16 +inv16 NBM CD34+ 2,0 1,0 0,0 Figure J: Expression of MYH11 as determined by Affymetrix GeneChip analyses in 285 cases of AML and controls. Expression levels of MYH11 were high in AML patients and inv(16), whereas low levels were detected in the other AML patients, CD34-positive cells and normal bone marrow.
13 FAB karyotype WBC FLT3 ITD FLT3 TKD AML-M3 t(15;17) Figure K: Snapshot of Correlation View showing the AML-M3 t(15;17) patients. FAB M2-purple, M3-orange, M4-yellow. Karyotype: normal-green, t(15;17)-orange, other-grey. The AML-M3 t(15;17) patients are divided into two groups, i.e., low white blood cell count (WBC) and FLT3 ITD 9 negative (green bar) versus high WBC/ FLT3 ITD positive (red bar). Karyotype is based on cytogenetics and WBC is depicted as 10 (cells/l).
14 ETO expression 40,0 35,0 30,0 25,0 20,0 15,0 -t(8;21) +t(8;21) NBM CD34+ 10,0 5,0 0,0 Figure L: Expression of ETO as determined by Affymetrix GeneChip analyses in 285 cases of AML and controls. Expression levels of ETO were high in AML patients and t(8;21), whereas low levels were detected in the other AML patients, CD34-positive cells and normal bone marrow.
15 Table A: Characteristics cluster #1 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 1595 #1 M1 NN #1 M1 NN #1 M1 Complex #1 M1 NN #1 M1 11q23 (t(4;11)) #1 M1 +11/11q23(sMLL) #1 M1 +11/+11/Other #1 M2 NN #1 M5 NN #1 M5 11q23 (t(11;19)) #1 M4 Other/11q23 (t(2;9;11)) #1 M1 11q23 (t(6;11)) #1 M5 11q23 (t(6;11)) #1 M5 NN
16 Table B: Characteristics cluster #2 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 3330 #2 M #2 M1 NN #2 ND NN #2 M4-9q #2 M4 NN #2 M4 t(6;9) #2 M4 NN #2 M5 NN #2 M5 NN #2 M1 NN #2 M5 NN #2 M4 NN #2 M2 NN #2 M4 NN ND 1551 #2 M1 NN #2 M4 NN #2 M
17 Table C: Characteristics cluster #3 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2480 #3 M1 NN #3 M2 NN #3 M1 NN #3 M2 NN #3 M2 NN #3 M1 NN #3 M1 NN #3 M1 NN #3 M1 NN #3 M2 t(9;22) #3 M1 +8/Other #3 M4 NN - ND #3 M4-7/11q #3 M2 t(6;9)/other #3 M5 t(6;9) #3 M1 NN #3 M2 NN #3 M #3 M2 ND
18 Table D: Characteristics cluster #4 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 3327 #4 M1 NN #4 M1-9q #4 M0 Complex #4 M1 NN #4 ND Complex (+8, +11) #4 M1 NN #4 M1 Other #4 M1 NN #4 M1 NN/11q23 (smll) #4 M1 NN #4 M1 NN #4 M1 NN #4 M1 NN #4 M1-9q #4 M1 NN
19 Table E: Characteristics cluster #5 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 3301 #5 M5-5/7(q) #5 M4 NN #5 M5 +8/Other #5 M5 NN - - ND ND #5 M4 ND #5 M5 NN #5 M4 +8/Other #5 M4 NN #5 M4 Complex #5 M #5 M5 Other #5 M5 +8/Other #5 M4 NN #5 M4 +8/Other #5 M5 NN #5 M4 NN #5 M5 ND #5 M5 +8/3q/Other #5 M4 NN #5 M5 NN #5 M5 NN #5 M4 NN #5 ND NN
20 Table E: Characteristics cluster #5 (continued) (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K-RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 3321 #5 M #5 M5 Other #5 M5 NN #5 M4 NN #5 M5 NN/11q23 (smll) #5 M5 NN #5 M5 NN #5 M5 NN #5 M5 NN #5 M5 NN #5 M #5 M5 t(6;9) #5 M5 NN #5 M5 NN #5 M5 NN #5 M5 NN #5 M4 NN #5 M4 NN #5 M5 NN #5 M2 Complex #5 M0 Complex
21 Table F: Characteristics cluster #6 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2683 #6 M2 NN #6 M1 NN #6 M2 NN #6 M1 NN #6 M1 NN #6 M2 NN #6 M1 NN #6 M1 ND
22 Table G: Characteristics cluster #7 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 3310 #7 M2 NN #7 M3 NN #7 M1 NN #7 M1 NN #7 M1 NN #7 M2 NN #7 M2 Other #7 M6 NN #7 M1 NN #7 M6 Other #7 M6 NN #7 M5 NN #7 ND Other #7 M2 +8/Other #7 M2 Complex(3q/+8) #7 M1 NN #7 M2 NN #7 M3 ND
23 Table H: Characteristics cluster #8 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2223 #8 M #8 M5 Complex (-7(q)/+8) #8 M2 Complex (11q23 (t(8;11)), -5, 3q) #8 ND +11/Other #8 M2 NN #8 ND +8,-7(q) #8 M2 NN #8 M2 inv7(q)/other #8 M #8 M2 NN #8 M2 Other #8 M0 Other #8 M2 NN
24 Table I: Characteristics cluster #9 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, BP:inv(16) breakpoint, RT: real-time PCR for CBFβ-MYH11 (Primer CBFβ 5 -AAGACTGGATGGTATGGGCTGT-3 (sense), Primer 126REV 5 -CAGGGCCCGCTTGGA-3 (antisense), Probe CBFβ 6- FAM 5 -TGGAGTTTGATGAGGAGCGAGCCC-3 TAMRA); FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K-RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype BP RT FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 3277 #9 M1 idt(16) A #9 M4 idt(16) A #9 M4 idt(16)/-7(q) A #9 M5 idt(16) A #9 M4 idt(16) A #9 M4 idt(16) A #9 M4 NN A #9 M5 idt(16) A #9 M4 idt(16) A #9 M4 NN A #9 M4 idt(16) A #9 M4 idt(16) D #9 M4 idt(16) A #9 M4 idt(16) A #9 M5-7(q) A #9 M4 idt(16)/+8 A #9 M4 idt(16) A ND #9 M4 idt(16) A #9 ND idt(16) A #9 M4 idt(16) A #9 M4 NN A #9 M2 idt(16)/+8 A #9 M4 idt(16) A
25 Table J: Characteristics cluster #10 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2661 #10 M4 ND #10 M #10 M5-7/3q #10 M2-7(q) #10 M5 Other #10 M0 Other #10 M #10 M1 t(9;22) #10 M #10 M #10 M0 Other #10 M0-7/3q #10 M5 ND #10 M1-7(q) #10 M1 Other #10 ND ND #10 M #10 M2 NN #10 M #10 M1 NN #10 M1 Other #10 M1 Other
26 Table K: Characteristics cluster #11 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2209 #11 M4 Other #11 M4 NN #11 M5 Other #11 M5 NN #11 M2 NN #11 M1 NN #11 M5 NN #11 ND NN #11 M5 NN
27 Table L: Characteristics cluster #12 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR for PML-RARα (Primer PML3-for 5 -CCCCAGGAGCCCCGT-3 (sense), Primer PML-kbr 5 -CCTGCAGGACCTCAGCTCTT-3 (sense), Primer RAR4-rev 5 - AAAGCAAGGCTTGTAGATGCG-3 (antisense), Probe RARA 6-FAM 5 -AGTGCCCAGCCCTCCCTCGC-3 TAMRA); FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K-RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype RT FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2466 #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17)/other #12 M3 t(15;17)/other #12 M3 t(15;17) #12 M3 t(15;17)/other #12 M2 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 t(15;17) #12 M3 Other* #12 M4 t(15;17)/other #12 M3 t(15;17)/ *Full karyotype of patient 322: 46,XX, add(12)(p1?3).
28 Table M: Characteristics cluster #13 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR for AML1-ETO (Primer 821 For 5 -TCACTCTGACCATCACTGTCTTCA-3 (sense), Primer 821 Rev 5 -ATTGTGGAGTGCTTCTCAGTACGAT -3 (antisense), Probe ETO 6- FAM 5 -ACCCACCGCAAGTCGCCACCT -3 TAMRA); FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K-RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype RT FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2243 #13 M2 t(+8;21)/other #13 M4 t(+8;21) #13 M2 t(+8;21) #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other #13 M2 t(+8;21) #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other #13 M2 t(+8;21)/+8/other #13 M2 t(+8;21)/other #13 M2 t(+8;21) #13 M2 t(+8;21) #13 M2 t(+8;21)/other #13 M2 t(+8;21) #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other #13 M1 t(+8;21) #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other #13 M2 t(+8;21)/other
29 Table N: Characteristics cluster #14 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2536 #14 ND ND #14 M2 ND #14 M2 +8/Other #14 M2 11q23 (ND) #14 M2-5(q) #14 M1 Complex(-5/-7/+8) #14 M4 Complex #14 M #14 M2 NN #14 M5 NN
30 Table O: Characteristics cluster #15 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2767 #15 M1 ND #15 M4 NN #15 M1 NN #15 M2 NN #15 M2 Other #15 M2 NN #15 M2 NN #15 M1-7/Other
31 Table P: Characteristics cluster #16 (Patient: patient number, Cluster: cluster number (2856 probe sets); FAB: FAB subtype of AML; Karyotype: t(15;17), t(8;21), inv(16)/t(16;16),+8,+11,+21,-5(q),-7(q),t(9;22),3q abnormalities, 11q23 abnormalities (translocation/self fusion (smll)), complex(abnormalities involved) (>3abnormalities) and normal karyotype (NN) are indicated, RT: real-time PCR; FLT3 ITD: internal tandem duplication in FLT3; FLT3 TKD: tyrosine kinase domain mutation in FLT3; N- or K-RAS: mutation in codon 12,13 or 61 of N- or K- RAS; EVI1: EVI1 overexpression; CEPBA: mutation in CEBPA, ND: not determined). Patient Cluster FAB Karyotype FLT3 ITD FLT3 TKD N-RAS K-RAS EVI1 CEBPA 2225 #16 M4 NN #16 M5 Other #16 M5 Other #16 M5 +8/11q23 (t(11;19) #16 M5 11q23 (t(9;11)) #16 M5 Other/11q23 (t(9;11)) #16 M5 11q23 (t(9;11)) #16 M5 Other #16 M5 NN #16 M1 NN #16 M5 11q23 (t(9;11))/
32 Table Q: Frequency and percentage of cytogenetic and molecular abnormalities of all AML patients within each of the assigned clusters. All patients with a specific abnormality were considered, irrespective of the presence of additional abnormalities (NC: patients not assigned to any of the 16 clusters). Cluster #1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #12 #13 #14 #15 #16 NC total Patients in cluster Cytogenetics t(15;17) 18 (95) 18 (6) t(8;21) 22 (100) 22 (8) inv(16)/t(16;16) 19 (83) 19 (7) +8 2 (12) 1 (5) 1 (7) 7 (16) 2 (11) 2 (15) 2 (9) 1 (5) 1 (5) 1 (5) 3 (30) 1 (9) 2 (15) 26 (9) (14) 1 (7) 1 (2) 1 (8) 1 (5) 1 (8) 7 (2) (5) 1 (8) 2 (1) -5 1 (8) 1 (5) 1 (10) 3 (1) -5(q) 1 (10) 1 (<1) -7 1 (5) 1 (2) 1 (8) 5 (23) 1 (10) 1 (13) 1 (9) 2 (15) 13 (5) -7(q) 3 (23) 2 (9) 2 (9) 7 (2) 3q 1 (2) 1 (6) 1 (8) 2 (9) 1 (8) 6 (2) t(6;9) 1 (6) 2 (11) 1 (2) 4 (1) t(9;22) 1 (5) 1 (5) 2 (1) t(11q23) 6 (43) 1 (5) 2 (13) 1 (2) 1 (8) 1 (10) 5 (45) 2 (15) 19 (7) complex (>3 abn.) 1 (7) 2 (13) 3 (7) 1 (6) 2 (15) 2 (20) 11 (4) other 2 (14) 1 (6) 2 (11) 3 (20) 7 (16) 4 (22) 4 (31) 6 (27) 2 (22) 4 (21) 15 (68) 1 (10) 2 (25) 4 (36) 3 (23) 60 (21) normal 6 (43) 13 (76) 13 (68) 10 (67) 27 (61) 7 (88) 12 (67) 4 (31) 3 (13) 2 (9) 7 (78) 2 (20) 5 (63) 3 (27) 5 (38) 119 (42) ND 2 (5) 1 (13) 1 (6) 3 (14) 2 (20) 1 (13) 10 (4) Cluster #1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #12 #13 #14 #15 #16 NC total Patients in cluster Molecular markers FLT3-ITD 2 (14) 14 (82) 10 (53) 1 (7) 14 (32) 8 (100) 4 (22) 4 (18) 1 (11) 6 (32) 1 (5) 3 (30) 2 (25) 8 (62) 78 (27) FLT3-TKD 3 (18) 3 (16) 6 (14) 1 (13) 6 (26) 1 (5) 3 (33) 5 (26) 1 (5) 2 (20) 1 (13) 1 (9) 33 (12) N-RAS 1 (7) 4 (9) 1 (8) 8 (35) 3 (14) 2 (22) 3 (14) 1 (10) 1 (13) 2 (15) 26 (9) K-RAS 1 (7) 4 (9) 2 (25) 1 (4) 1 (5) 9 (3) EVI1 5 (36) 2 (11) 2 (5) 2 (11) 10 (45) 2 (15) 23 (8) CEBPA 1 (6) 8 (53) 1 (2) 1 (5) 1 (5) 5 (63) 17 (6)
33 Table A1: Top40 genes cluster #1 Probe Set ID Gene Symbol Locus Link Accession Score SAM _at LOC NM_ ,09 1, _at KCNA NM_ ,68 1, _at GPR AL ,18 1, _s_at TRPS NM_ ,95 1, _s_at BHLHB AB ,63 1, _at EVI BE ,40 1, _s_at KIAA NM_ ,96 1, _at IGHM 3507 X ,85 1, _at MMRN NM_ ,72 1, _at MEF2C 4208 N ,59 1, _at ATP10A AB ,41 1, _s_at FHL U ,37 1, _x_at PCDHGC NM_ ,29 1, _at KIF AA ,25 1, _s_at LTBP NM_ ,21 1, _s_at PCDHGC AK ,20 1, _at SPIB 6689 NM_ ,15 1, _s_at SOCS AB ,12 1, _x_at PCDHGC AF ,11 1, _at AF ,09 1, _s_at MEF2C 4208 N ,08 1, _s_at BLNK NM_ ,05 1, _s_at DPP M ,03 1, _s_at AI ,01 1, _s_at PROM NM_ ,97 1, _at SOCS NM_ ,95 1, _s_at SLC38A NM_ ,87 1, _at BMI1 648 NM_ ,86 1, _x_at FHL AF ,83 1, _s_at IRF NM_ ,77 1, _s_at SPAG AI ,77 1, _s_at SLC2A AA ,76 1, _s_at NR4A AI ,80 1, _s_at NR4A S ,84 1, _s_at SLC2A AL ,85 1, _x_at NR4A NM_ ,85 1, _x_at SLC2A NM_ ,91 1, _x_at JUN 3725 BG ,92 1, _s_at ATF3 467 NM_ ,11 1,96 q-value SAM (%)
34 Table B1: Top 40 genes cluster #2 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _s_at GLI NM_ ,30 1, _at IL2RA 3559 NM_ ,15 1, _s_at IL2RA 3559 K ,24 1, _at TRPC AI ,44 1, _at PLS NM_ ,34 1, _at PLA2G4A 5321 M ,31 1, _at TRIM NM_ ,23 1, _s_at PTP4A NM_ ,01 1, _at DOCK NM_ ,48 1, _s_at KCNK NM_ ,29 1, _at LPIN D ,05 1, _at RhoGAP NM_ ,82 1, _at CCL NM_ ,69 1, _s_at GPR NM_ ,41 1, _s_at GOLGIN AI ,37 1, _at HOXB NM_ ,12 1, _at GPR AL ,01 1, _at GRB D ,99 1, _x_at GOLGIN AF ,97 1, _s_at LAPTM4B AW ,95 1, _s_at GUCY1A AI ,95 1, _at PIM M ,94 1, _s_at SCHIP NM_ ,89 1, _at HOXA NM_ ,74 1, _x_at GOLGIN AF ,70 1, _s_at JAG1 182 U ,68 1, _s_at CLU 1191 M ,60 1, _x_at V ,62 1, _x_at HBA AF ,67 1, _x_at AF ,71 1, _x_at HBB 3043 M ,71 1, _x_at HBA T ,72 1, _x_at HBB 3043 AF ,72 1, _x_at HBA BC ,75 1, _x_at HBA NM_ ,83 1, _s_at VIL J ,91 1, _x_at HBA AF ,96 1, _at PDE3B 5140 NM_ ,29 1, _s_at AI ,39 1, _s_at MAP4K NM_ ,87 1,04
35 Table C1: Top40 genes cluster #3 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _at SCN9A 6335 NM_ ,09 0, _at GAS NM_ ,63 0, _at CCL NM_ ,56 0, _at PLS NM_ ,94 0, _s_at COL4A AW ,51 0, _s_at LAPTM4B AW ,09 0, _at RhoGAP NM_ ,07 0, _s_at LAPTM4B NM_ ,05 0, _at QPRT NM_ ,04 0, _x_at ANPEP 9053 T ,84 0, _at LOC NM_ ,81 0, _at SMC4L AL ,81 0, _at SH2D1A 4068 AF ,74 0, _at ADCY2 108 AU ,53 0, _s_at ENPP AW ,48 0, _at TRIM NM_ ,42 0, _s_at LAPTM4B T ,41 0, _s_at GPR NM_ ,28 0, _at MAP T ,28 0, _s_at MAP AJ ,23 0, _s_at FLJ NM_ ,20 0, _s_at SCDGF-B NM_ ,05 0, _at DOCK NM_ ,03 0, _s_at HFL X ,00 0, _s_at SMC4L NM_ ,00 0, _x_at TNFRSF AJ ,96 0, _s_at SEPP NM_ ,94 0, _x_at PBXIP NM_ ,92 0, _at NET AW ,85 0, _at C14orf NM_ ,85 0, _s_at KIAA NM_ ,88 0, _at IL17R NM_ ,95 0, _at IL6ST 3572 AL ,03 0, _at SERPINB NM_ ,11 0, _x_at BLVRA 644 NM_ ,71 0, _at RAP2A 5911 AI ,94 0, _s_at FCGRT 2217 NM_ ,10 0, _x_at BLVRA 644 BC ,18 0, _s_at AGTPBP NM_ ,15 0, _at AIM1 202 U ,19 0,21
36 Table D1: Top40 genes cluster #4 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _at AV ,34 0, _s_at 6964 X ,01 0, _s_at B4GALT NM_ ,59 0, _at 6964 AW ,85 0, _x_at UGT2B AF ,60 0, _at FLJ NM_ ,57 0, _s_at 6964 X ,55 0, _s_at CD7 924 NM_ ,22 0, _x_at CD7 924 AI ,04 0, _at IGFBP AW ,85 0, _s_at C18orf1 753 NM_ ,65 0, _at ZNFN1A NM_ ,27 0, _s_at ABCB AF ,90 0, _at B4GALT AF ,66 0, _s_at TRIM AJ ,44 0, _at ABCB AF ,40 0, _s_at P2RX U ,36 0, _x_at PMS2L D ,20 0, _at HPS AL ,16 0, _at PGDS NM_ ,79 0, _at TM4SF NM_ ,79 0, _at FZD NM_ ,63 0, _at BG ,50 0, _at ITGA NM_ ,49 0, _at ITGA BG ,37 0, _at FLJ NM_ ,51 0, _at CYFIP BC ,75 0, _s_at KLF NM_ ,95 0, _at IL4R 3566 NM_ ,96 0, _s_at DF 1675 NM_ ,98 0, _at CAPN2 824 M ,08 0, _s_at CSDA 8531 AL ,13 0, _at LRP NM_ ,19 0, _at RAB NM_ ,25 0, _s_at NDFIP NM_ ,98 0, _at C8FW NM_ ,41 0, _at TUBB BC ,60 0, _x_at CTNNA NM_ ,35 0, _s_at CTNNA AI ,70 0, _x_at CTNNA D ,91 0,11
37 Table E1: Top40 genes cluster #5 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _s_at EPB41L NM_ ,03 0, _s_at LILRB NM_ ,91 0, _s_at EPB41L BC ,65 0, _at SIRPB NM_ ,55 0, _at PILRA NM_ ,93 0, _at CAMK NM_ ,41 0, _at DKFZp434L NM_ ,11 0, _at EPB41L AI ,04 0, _s_at UBE2D AL ,87 0, _s_at VDR 7421 NM_ ,69 0, _s_at STS 412 AU ,64 0, _s_at SIGLEC NM_ ,61 0, _at PTAFR 5724 D ,55 0, _s_at CSPG BF ,07 0, _at PHT NM_ ,04 0, _at TLR NM_ ,94 0, _x_at LILRB AF ,91 0, _s_at PILRA AJ ,71 0, _s_at STS 412 AU ,70 0, _s_at ECGF NM_ ,70 0, _at LILRB AF ,70 0, _x_at HNMT 3176 BC ,69 0, _s_at MGC NM_ ,67 0, _s_at KCNQ NM_ ,66 0, _at IFNGR NM_ ,58 0, _at CARD NM_ ,53 0, _x_at LILRB NM_ ,46 0, _at CD BG ,21 0, _s_at CD NM_ ,15 0, _s_at STS 412 NM_ ,05 0, _at GNS 2799 AW ,03 0, _at RASSF AF ,00 0, _s_at MAFB 9935 NM_ ,99 0, _at ASM3A AA ,96 0, _x_at LILRB AF ,91 0, _x_at LILRB NM_ ,90 0, _s_at PSAP 5660 M ,89 0, _s_at CCR NM_ ,87 0, _s_at EPHB D ,85 0, _at TFEB 7942 AI ,81 0,05
38 Table F1: Top40 genes cluster #6 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _s_at AI ,39 0, _at AI ,99 0, _s_at SNCAIP 9627 NM_ ,81 0, _at FTO U ,51 0, _at MGC AK ,40 0, _at GPC NM_ ,34 0, _s_at GPC AF ,25 0, _at DKFZP564M AK ,56 0, _s_at PLXNB AV ,42 0, _s_at FLJ NM_ ,93 0, _at FLJ NM_ ,80 0, _at ADCY2 108 AU ,78 0, _at FLJ NM_ ,78 0, _s_at LTBP AI ,64 0, _at FOXF NM_ ,60 0, _at VLCS-H NM_ ,31 0, _at FOXC AU ,23 0, _x_at SMC4L AK ,19 0, _s_at DPYSL NM_ ,18 0, _s_at HOXB NM_ ,17 0, _at NM_ ,16 0, _s_at DSC BF ,16 0, _at BITE NM_ ,13 0, _s_at HFL X ,12 0, _at NM_ ,08 0, _at CAT 847 AU ,04 0, _x_at DSC NM_ ,01 0, _s_at LTBP NM_ ,97 0, _at BF ,61 0, _at BST2 684 NM_ ,55 0, _x_at HLA-DRB AJ ,56 0, _at CD K ,58 0, _at PECAM AW ,62 0, _s_at HLA-DRA 3122 M ,68 0, _at HLA-DPA M ,84 0, _s_at KIAA AK ,87 0, _at XPA 7507 NM_ ,10 0, _x_at HIG NM_ ,41 0, _s_at RGS NM_ ,69 0, _at CORO1A U ,97 0,85
39 Table G1: Top40 genes cluster #7 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _s_at TPM NM_ ,29 0, _at GYPE 2996 NM_ ,28 0, _x_at PLAB 9518 AF ,76 0, _at TRIM X ,56 0, _s_at ANK1 286 NM_ ,78 0, _s_at DNAJC AV ,68 0, _s_at RHAG 6005 AF ,40 0, _x_at MYL X ,18 0, _x_at MYL M ,16 0, _x_at ANK1 286 M ,09 0, _s_at SLC6A NM_ ,08 0, _at TNS 7145 AF ,98 0, _at RAP1GA NM_ ,94 0, _x_at EPB AF ,93 0, _at HBZ 3050 NM_ ,90 0, _x_at RHAG 6005 AF ,88 0, _x_at ANK1 286 NM_ ,84 0, _x_at ANK1 286 NM_ ,83 0, _at MAP NM_ ,71 0, _s_at SPTB 6710 NM_ ,70 0, _x_at ANK1 286 NM_ ,70 0, _at KCNH NM_ ,67 0, _x_at MYL AF ,65 0, _x_at RHD 6007 AF ,64 0, _x_at SLC6A U ,61 0, _s_at C5orf NM_ ,60 0, _at N ,60 0, _x_at X ,53 0, _at RHAG 6005 NM_ ,51 0, _x_at SLC6A AW ,48 0, _at KEL 3792 NM_ ,47 0, _s_at TAL X ,42 0, _s_at OSBP NM_ ,37 0, _s_at DKFZP434C AK ,27 0, _s_at EPB NM_ ,24 0, _s_at ANK1 286 AI ,21 0, _at SLC2A NM_ ,20 0, _s_at SELENBP NM_ ,18 0, _s_at MSCP NM_ ,13 0, _at CLCN NM_ ,12 0,11
40 Table H1: Top40 genes cluster #8 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _at RIS BF ,86 0, _s_at CDH1 999 NM_ ,12 0, _at ABCG AF ,01 0, _at OPTN AV ,88 0, _at LU 4059 X ,45 0, _at PBX BF ,14 0, _s_at ARHGEF NM_ ,95 0, _x_at RHD 6007 L ,72 0, _x_at ANK1 286 M ,53 0, _s_at OSBP NM_ ,53 0, _at CDC42BPA 8476 NM_ ,44 0, _s_at C5orf NM_ ,42 0, _at MXI NM_ ,29 0, _s_at GYPA 2993 BC ,22 0, _x_at ANK1 286 NM_ ,20 0, _s_at ALS2CR NM_ ,10 0, _at AA ,06 0, _x_at L ,04 0, _at GYPA 2993 NM_ ,04 0, _at SLC6A NM_ ,03 0, _s_at TAL X ,98 0, _at CDC42BPA 8476 NM_ ,96 0, _x_at GYPA 2993 U ,95 0, _at TNS 7145 AF ,94 0, _s_at U ,90 0, _s_at OPTN NM_ ,89 0, _at WDR NM_ ,86 0, _x_at GYPE 2996 U ,84 0, _s_at ALS2CR AV ,84 0, _x_at RHCE 6006 X ,81 0, _s_at SNCA 6622 NM_ ,80 0, _x_at ANK1 286 NM_ ,78 0, _x_at SLC6A AW ,78 0, _x_at RHD 6007 AF ,77 0, _at TM4SF AF ,75 0, _s_at DJ473B NM_ ,74 0, _s_at SELENBP NM_ ,70 0, _r_at C5orf H ,70 0, _x_at ANK1 286 NM_ ,69 0, _at FECH 2235 AU ,66 0,17
41 Table I1: Top40 genes cluster #9 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _x_at MYH NM_ ,02 0, _x_at MYH NM_ ,72 0, _at CLIPR AL ,92 0, _at ST NM_ ,69 0, _at NRP BE ,71 0, _at CLECSF NM_ ,32 0, _s_at PAPSS AF ,04 0, _s_at PAPSS AW ,73 0, _at CD1C 911 NM_ ,82 0, _s_at COLEC NM_ ,69 0, _s_at MSLN NM_ ,36 0, _s_at CHI3L M ,06 0, _at FLJ NM_ ,59 0, _s_at CRA NM_ ,49 0, _at CHI3L M ,07 0, _s_at AK NM_ ,88 0, _s_at ICAM NM_ ,76 0, _at Z39IG NM_ ,23 0, _s_at SPARC 6678 NM_ ,18 0, _at TGFBI 7045 NM_ ,99 0, _at RPS6KA AI ,82 0, _at NT5E 4907 NM_ ,67 0, _at MN NM_ ,24 0, _at SDR NM_ ,92 0, _at LOC AU ,85 0, _s_at FCGR2B 2213 M ,82 0, _at CGI NM_ ,45 0, _at PTPRM 5797 NM_ ,25 0, _s_at RUNX3 864 NM_ ,25 0, _s_at CD NM_ ,33 0, _s_at NDE NM_ ,42 0, _at EMU AL ,56 0, _s_at RUNX3 864 AA ,85 0, _s_at MGLL BC ,01 0, _at FLJ NM_ ,61 0, _s_at CBFB 865 AF ,73 0, _s_at CHST NM_ ,82 0, _s_at CYLN BC ,24 0, _s_at CBFB 865 NM_ ,01 0, _at CD NM_ ,28 0,18
42 Table J1: Top40 genes cluster #10 Probe Set ID Gene Symbol Locus Link Accession Score SAM q-value SAM (%) _at FLJ NM_ ,59 0, _s_at CRIM BG ,82 0, _at FLJ AI ,75 0, _at NRLN AL ,99 0, _s_at SPTBN NM_ ,75 0, _at FLJ AL ,75 0, _at AI ,74 0, _at SETBP NM_ ,63 0, _at F2RL BE ,53 0, _at PPP1R16B AB ,52 0, _s_at LOC BC ,51 0, _at GDAP1L BF ,43 0, _s_at SCAM NM_ ,42 0, _s_at TPM NM_ ,21 0, _at RBPMS D ,19 0, _s_at RBPMS NM_ ,14 0, _at PRKD AF ,14 0, _at SPON AB ,12 0, _at PIK3C2B 5287 NM_ ,11 0, _at PPP1R16B AB ,09 0, _at MN NM_ ,03 0, _at GNAI AL ,02 0, _at C14orf NM_ ,91 0, _at P164RHOGEF 9828 NM_ ,89 0, _x_at SPTBN NM_ ,88 0, _at IGHM 3507 X ,86 0, _s_at SPON AB ,74 0, _s_at MLLT AV ,59 0, _at EEF1A NM_ ,57 0, _s_at FLNB 2317 M ,40 0, _at CD NM_ ,29 0, _at NPDC NM_ ,25 0, _s_at RBPMS D ,21 0, _s_at BAALC NM_ ,11 0, _s_at BCL7A 605 AI ,05 0, _s_at SPTBN BE ,93 0, _at RNASE NM_ ,00 0, _at C3AR1 719 U ,34 0, _s_at DF 1675 NM_ ,63 0, _s_at AZU1 566 NM_ ,95 0,21
Molecular evolutionary dynamics of respiratory syncytial virus group A in
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