DNA damage repair alterations are frequent in prostatic adenocarcinomas with focal pleomorphic giant‐cell features

Autor:	Abdullah M Alharbi, Harsimar B. Kaur, Tamara L. Lotan, Colin C. Pritchard, Jonathan I. Epstein
Rok vydání:	2019
Předmět:	Adult Male 0301 basic medicine Histology DNA repair Adenocarcinoma MLH1 DNA Mismatch Repair Giant Cells Article Germline Pathology and Forensic Medicine 03 medical and health sciences Prostate cancer 0302 clinical medicine Humans Medicine Aged Aged 80 and over business.industry Prostatic Neoplasms General Medicine Mismatch Repair Protein medicine.disease Immune checkpoint 030104 developmental biology MSH2 030220 oncology & carcinogenesis Mutation Cancer research DNA mismatch repair business DNA Damage
Zdroj:	Histopathology
ISSN:	1365-2559 0309-0167
DOI:	10.1111/his.13806
Popis:	Aims Prostatic adenocarcinomas with focal pleomorphic giant-cell features constitute a rare tumour subtype with abysmal clinical outcomes. More than one-third of patients with this histology die within a year of the initial diagnosis of prostate cancer. We aimed to perform molecular profiling of these tumors to identify potential therapeutic targets. Methods and results Here, we performed next-generation sequencing with a highly validated targeted panel (UW-OncoPlex) on somatic tumour DNA extracted from eight cases of prostatic adenocarcinoma with focal pleomorphic giant-cell features, including cases with and without prior treatment for prostate cancer. We found that DNA damage repair mutations are common in this rare subset of prostate tumours, with two of eight having bi-allelic pathogenic mutations in homologous DNA repair genes (including BRCA2 and NBN) and two of eight having bi-allelic pathogenic mutations in mismatch repair genes (including MSH2 and MLH1). Conclusion These data are consistent with emerging data showing that DNA repair alterations are enriched among castration-resistant prostate cancer and aggressive subsets of primary tumours. Given that these patients are potential candidates for poly(ADP-ribose) polymerase inhibitor and/or immune checkpoint blockade, and have a poor prognosis with standard therapy, we recommend that tumour and germline DNA sequencing with or without mismatch repair protein immunohistochemistry be considered for all prostatic adenocarcinomas with focal pleomorphic giant-cell features.
Databáze:	OpenAIRE
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