Biallelic tumour suppressor loss and DNA repair defects in de novo small-cell prostate carcinoma

The Journal of Pathology
Edmund Cp ChedgyAlexander W Wyatt

Abstract

Small-cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small-cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life-expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first-line platinum-based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin-embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment-related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2...Continue Reading

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Citations

Apr 10, 2020·Frontiers in Oncology·Yuichiro HatanoAkira Hara
Apr 30, 2020·Orphanet Journal of Rare Diseases·Katie KerrAmy Jayne McKnight
Nov 21, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elie RitchAlexander W Wyatt
Jan 13, 2021·Current Oncology Reports·Yasutaka Yamada, Himisha Beltran
Jan 17, 2021·Prostate Cancer and Prostatic Diseases·Takayuki SumiyoshiAlexander W Wyatt
May 27, 2020·European Urology·Cameron HerbertsAlexander W Wyatt
Jul 23, 2021·Nature Reviews. Urology·Yong WangYuzhuo Wang
Dec 23, 2021·Nature Communications·Neha SinghAndrew S Kraft

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