Table 1.

Clinical MPN samples studied

BROCA Analysisc,e,f
MPN #Clinical diagnosisaKaryotypeBRCA1 MethylationbJAK2 V617F Mutb,cRAD51 Foci formationc,dH2Ax Foci formationcVeliparib IC50 (μmol/L)Olaparib IC50 (μmol/L)Deleterious alterationsVariants of unknown significance
1Post-ET MF46XYNoNormalNormal6.9cCHEK2 c.1100delGNone
2PMF46XY 11q−+15
3PMFg7XY 13q− +14NoImpairedNormal1.30.35NoneLIG4 p.A857T PALB2 p.R414Q
4PMF46XX 5q−No48%NormalNormal8.60.83NonePRKDC p.M333I RAD51D p.R232Q
5PV46XY inv9Yes+1.00.56NoneCDK12 p.P1275L, MSH2 p.R55G
7MDS/MPN-U47XY +1pYesNormalNormal2.40.64NonePRKDC p.P695S TP53BP1 p.V1031A
8Post-PV MF47XY +845%NormalNormal9.31.8
9MDS/MPN-U46XYNoImpairedImpaired0.80.14NoneNo alterations
11tPVa46XY t(11;14)+NormalNormal>205.2
14PMF47XX +9 t(12;13)+ImpairedNormal7.01.1
15CML45X −Y t(9;22)ImpairedImpaired2.2
16PMF46XX 20q-+2.7NonePRKDC p.A3904V
21tCMMoLa46XYNo4.1NoneNo alterations
22CMMoL46,XY,del(2)(q)No1.3NoneXRCC4c.24delC DCLRE1C p.G38R
23CMMoL46XXYes2.5NonePIK3CA p.Y644H
24tPMFa92XXYY der2 t(1;2)+4.1
27PMF45X −YYes+5.4NoneSLX4 p.P385T, p.P957L, p.E942Q
29CML46XX t(9;22)No4.0NoneMSH6p. I1054F PTEN p.H397R
30aCML eo46XX t(4;7)No4.4NoneCDK12 p.L988S, NBN p.I439M SLX4 p.R1372Q and p.A916S
31CMMoL46XXNo2.2BRCA1 5382insC (c.5263_5264insC)RAD51B p.K243R TOPBP1 p.N1042S,
32PMF46XY t(1;7) +9 1q−Yes+4.2NoneTOPBP1 p.R309C XRCC5 p.A550S
33PMF46 XYNo+1.7NoneLIG4 p.T9I
34CMMoL48 XY +8 +14No0.8NoneCDK12 p.L1189Q MLH1 p.H718Y, PALB2 p.D134N, PRKDC p.R1253H, SLX4 p.E701D, TOPBP1p.M293V
35CMMoL46 XXNo34%1.5NoneXRCC5 p.R184H
36CMMoL46 XYYes4.3NoneATR L274F, RBBP8 C485
37PMF46 XY 20q−No+1.9NoneBARD1 p.Q11H, BLM p.I366T, PIK3CA p.R524K
38CMMoL46 XYNo4.3RAD50 c.3476delAATR p.H117R, CDK12 p.P645S, NBN p.N142S, SLX4 p.S1271F, UIMC1 p.Y564H
39CML46 XY t(9:22)4.8NoneATR p.I97F, MRE11 p.S334R, RBBP8 p.K357N, SLX4 p.K1635E, TP53BP1 p.H58R
40CMMoL46 XYNo3.2NoneATM p.S1691R, FAM175A p.T141I, TOPBP1 p.S817L, TP53BP1 p.E1019G
41ET46 XY43%3.80.78
  • Abbreviations: aCML eo, associated with eosinophilia; ET, essential thrombocythemia; MF, myelofibrosis; PMF, primary myelofibrosis; PV, polycythemia vera; U, unclassifiable.

  • at, transformed to AML at the time of study.

  • b+, JAK2 V617F mutation present; −, tested and mutation not present; numbers indicate quantitative allele burden where available.

  • cBlank cell indicates assay not performed.

  • dNormal, foci form normally in response to ionizing radiation; impaired, foci form in fewer cells after ionizing radiation. See Fig. 1 for quantitation.

  • eSequence alterations deleterious to HR genes (bold) or nonhomologous end-joining (underlined) are shown here. Additional variants of unknown significance (previously reported allelic polymorphisms in the normal population at allele frequencies from 0.0005–0.24 and conservative substitutions) are listed in Supplementary Table S2.

  • fAll nomenclature is according to Human Genome Variation Society (HGVS) nomenclature except for the BRCA1 alteration, for which Breast Cancer Information Core nomenclature is provided, along with the the HGVS nomenclature in parentheses.

  • gMissing 1 copy of BRCA2 as a consequence of the 13q deletion.