Table 1.

Clinical MPN Samples Studied

MPN #	Clinical Diagnosisa	Karyotype	BRCA1 methylationc	JAK2 V617F Mutb,c	RAD51 foci Formationb,d	H2Ax foci formationb,	Veliparib IC50 (μM)	Olaparib IC50 (μM)	BROCA analysisb,e,f
									Deleterious alterations	Variants of unknown significance
1	Post-ET MF	46XY	No	−	Normal	Normal	6.9	b	CHEK2 c.1100delG	None
2	PMF	46XY 11q-		+			15
3	PMFg	7XY 13q- +14	No	−	Impaired	Normal	1.3	0.35	None	LIG4 p.A857T PALB2 p.R414Q
4	PMF	46XX 5q-	No	48%	Normal	Normal	8.6	0.83	None	PRKDC p.M333I RAD51D p.R232Q
5	PV	46XY inv9	Yes	+			1.0	0.56	None	CDK12 p.P1275L, MSH2 p.R55G
6	CMMoL	46XX		−	Impaired	Normal	4.8	0.4
7	MDS/MPN-U	47XY +1p	Yes	−	Normal	Normal	2.4	0.64	None	PRKDC p.P695S TP53BP1 p.V1031A
8	Post-PV MF	47XY +8		45%	Normal	Normal	9.3	1.8
9	MDS/MPN-U	46XY	No	−	Impaired	Impaired	0.8	0.14	None	No alterations
10	CMMoL	46XY		−	impaired	Normal	0.7	1.0
11	tPV	46XY t(11;14)		+	Normal	Normal	>20	5.2
12	CMMoL	46XY		−	Normal	Normal	2.6	0.30
13	PMF	46XY		58%	Normal	Normal	22	1.8
14	PMF	47XX +9 t(12;13)		+	Impaired	Normal	7.0	1.1
15	CML	45X -Y t(9;22)			Impaired	Impaired	2.2
16	PMF	46XX 20q-		+			2.7		None	PRKDC p.A3904V
17	ET			−	Normal	Normal	2.9
18	ET			+			0.3
19	ET			+			4.6
20	CMMoL	46XY	No	−			ovgrth
21	tCMMoL	46XY	No				4.1		None	No alterations
22	CMMoL	46,XY,del(2)(q)	No	−			1.3		XRCC4 c.24 delC	XRCC4 c.24 delC DCLRE1C p.G38R
23	CMMoL	46XX	Yes				2.5		None	PIK3CA p.Y644H
24	tPMF	92XXYY der2 t(1;2)		+			4.1
25	CMMoL	46XY	No	−			3.2
26	CMMoL	46XX					5.5
27	PMF	45X -Y	Yes	+			5.4		None	SLX4 p.P385T, p.P957L, p.E942Q
28	CMMoL	46XY	No	−			1.9
29	CML	46XX t(9;22)	No				4.0		None	MSH6p. I1054F PTEN p.H397R
30	aCML eo	46XX t(4;7)	No				4.4		None	CDK12 p.L988S, NBN p.I439M SLX4 p.R1372Q and p.A916S
31	CMMoL	46XX	No				2.2		BRCA1 5382insC (c.5263_5264insC)	RAD51B p.K243R TOPBP1 p.N1042S,
32	PMF	46XY t(1;7) +9 1q-	Yes	+			4.2		None	TOPBP1 p.R309C XRCC5 p.A550S
33	PMF	46 XY	No	+			1.7		None	LIG4 p.T9I
34	CMMoL	48 XY +8 +14	No				0.8		None	CDK12 p.L1189Q MLH1 p.H718Y, PALB2 p.D134N, PRKDC p.R1253H, SLX4 p.E701D, TOPBP1p.M293V
35	CMMoL	46 XX	No	34%			1.5		None	XRCC5 p.R184H,
36	CMMoL	46 XY	Yes	−			4.3		None	ATR L274F, RBBP8 C485
37	PMF	46 XY 20q-	No	+			1.9		None	BARD1 p.Q11H, BLM p.I366T, PIK3CA p.R524K
38	CMMoL	46 XY	No				4.3		RAD50 c.3476delA	ATR p.H117R, CDK12 p.P645S, NBN p.N142S, SLX4 p.S1271F, UIMC1 p.Y564H
39	CML	46 t(9:22)		−			4.8		None	ATR p.I97F, MRE11 p.S334R, RBBP8 p.K357N, SLX4 p.K1635E, TP53BP1 p.H58R
40	CMMoL	46 XY	No	−			3.2		None	ATM p.S1691R, FAM175A p.T141I, TOPBP1 p.S817L, TP53BP1 p.E1019G
41	ET	46 XY		43%			3.8	.78

^aAbbreviations used are: MF, myelofibrosis; CMMoL, chronic myelomonocytic leukemia; ET, essential thrombocythemia; PMF, primary myelofibrosis; PV, polycythemia vera; and t, transformed to AML at the time of study.

^bBlank cell indicates assay not performed.

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

^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 to 0.24 and conservative substitutions) are listed in Table S2

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

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