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Nearly one in ten of 289 unselected patients with resected pancreatic cancer carried an inherited cancer-gene variant, but the tumour had lost the second copy in fewer than half, which matters for whether PARP inhibitors will work.
Germline and somatic DNA from 289 patients with resected pancreatic ductal adenocarcinoma, ascertained without preselection, were analysed on a customised panel. 28 of 289 (9.7%) carried pathogenic or likely pathogenic germline variants: 21 (7.3%) in double-strand DNA damage repair genes (3 BRCA1, 4 BRCA2, 14 in ATM, BRIP1, CHEK2, NBN, PALB2, RAD50 or RAD51C), 3 Lynch syndrome and 4 other (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry found second hits in 12 of 27 (44.4%). Carriers of double-strand repair variants had superior overall survival (hazard ratio 0.54).
A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.
Shares ATM, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm), CDKN2A.
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm), Germline vs somatic mutations.
Shares ATM, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm), BRCA or PALB2-mutant pancreatic ductal adenocarcinoma.
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, ATM, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm).
Shares Andrew J. Aguirre, Germline vs somatic mutations, Dana-Farber Brigham Cancer Center, BRCA1 / BRCA2 (HRD).
Shares ATM, Germline BRCA1/2 pathogenic variant (gBRCAm), CDKN2A, Germline vs somatic mutations.
Shares ATM, PALB2, CDKN2A, Germline vs somatic mutations.
Shares ATM, CDKN2A, BRCA1 / BRCA2 (HRD), Germline (hereditary) testing.