In a pan-cancer analysis, patients with pancreatic acinar cell carcinoma (PACC) had the highest prevalence of BRCA2 germline pathogenic variants.

In fact, researchers found that patients with PACC had the highest prevalence of germline pathogenic variants in homologous recombination (HR) and DNA damage response (DDR) genes overall. The researchers reported these findings in the Journal of Clinical Oncology.

For this study ( Identifier: NCT01775072), researchers used the MSK-IMPACT assay to examine tumor samples from 28,780 patients with cancer, of whom 49 were diagnosed with PACC. Thirty-one patients with PACC (63%) had a pure acinar cell phenotype, and 18 (37%) had mixed acinar cell histology.

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There were 18 patients with PACC who had pathogenic or likely pathogenic variants in HR and DDR genes, including BRCA1 (1 patient), BRCA2 (12 patients), PALB2 (2 patients), ATM (2 patients), and CHEK2 (1 patient).

Germline alterations in these 5 genes were significantly more common in patients with PACC (36.7%) than in those with other cancers, including high-grade serous ovarian cancer (15.1%), breast cancer (8.6%), pancreatic ductal adenocarcinoma (PDAC; 8.1%), and prostate cancer (8.1%).

Almost half (48%) of the patients with pure PACC had a germline pathogenic variant affecting HR/DDR-related genes. “[T]hese alterations are likely etiologically linked to the development of the cancer given the consistent observation of genomic features of HRD in the pure PACCs harboring BRCA2 and PALB2 germline pathogenic variants,” the researchers wrote.

The prevalence of BRCA2 germline pathogenic variants was significantly higher in patients with pure PACC (35%) than in those with high-grade serous ovarian carcinoma (5.1%), prostate cancer (3.4%), PDAC (3.1%), or breast cancer (2.5%).

These findings suggest that “PACC should be considered as part of the spectrum of BRCA-related malignancies,” the researchers concluded.

“Patients with PACC should routinely undergo genetic testing given the high prevalence of pathogenic germline HR/DDR mutations, which may help inform both therapeutic and screening strategies,” Andrew H. Ko, MD, an associate editor for the journal wrote in a comment on the findings.

Disclosures: This research was partly supported by Repare Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mandelker D, Marra A, Zheng-Lin B, et al. Genomic profiling reveals germline predisposition and homologous recombination deficiency in pancreatic acinar cell carcinoma. J Clin Oncol. Published online August 22, 2023. doi:10.1200/JCO.23.00561