Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells. Issue 2 (February 2022)

• Record Type: Journal Article
• Authors: Tadehara, Masayoshi; Kato, Takuya; Adachi, Kai; Tamaki, Akihiro; Kesen, Yurika; Sakurai, Yasutaka; Ichinoe, Masaaki; Koizumi, Wasaburo; Murakumo, Yoshiki
• Is Part Of: Pancreas. Volume 51:Issue 2(2022)
• Page Start: 183
• Page End: 189
• Publication Date: 2022-02
• Subjects: BRCAness -- cisplatin -- KP-2 -- MLPA -- olaparib -- pancreatic cancer; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000001975
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objective: The concept of BRCAness has been proposed as a homologous recombination repair dysfunction triggered by a genetic defect in the BRCA pathway including the BRCA1/2 mutations. A certain number of pancreatic ductal adenocarcinoma (PDAC) patients have BRCAness. However, a large-scale analysis of BRCAness in PDAC has not been performed. In addition, no basic studies have examined the significance of BRCAness in PDAC cell lines. Methods: Ninety-two patients who underwent surgery for PDAC were enrolled. Formalin-fixed and paraffin-embedded specimens of resected PDACs were used to analyze BRCAness by multiplex ligation-dependent probe amplification. We also analyzed BRCAness in pancreatic cancer cell lines and the sensitivity to cisplatin and olaparib using a colony formation assay. Results: Of the 92 patients with PDAC, 6 were detected to have BRCAness-positive PDAC (6.5%). No significant differences in overall survival and progression-free survival were observed between the BRCAness-positive and BRCAness-negative groups. One PDAC cell line, KP-2, was positive for BRCAness and was more sensitive to cisplatin and olaparib than the BRCAness-negative cell lines. Conclusions: Our results revealed that a considerable number of PDACs are positive for BRCAness, suggesting that BRCAness status could be a useful biomarker for selecting anticancer treatments for advanced or relapsed PDAC.