Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells
Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells
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可切除胰腺导管腺癌中 BRCA 的临床病理意义及其与胰腺癌细胞抗癌药物敏感性的关系
DOI：
10.1097/mpa.0000000000001975
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发表时间：
2022
期刊：
影响因子：
2.9
通讯作者：
Murakumo Yoshiki
中科院分区：
文献类型：
--
作者：
Tadehara Masayoshi;Kato Takuya;Adachi Kai;Tamaki Akihiro;Kesen Yurika;Sakurai Yasutaka;Ichinoe Masaaki;Koizumi Wasaburo;Murakumo Yoshiki
目的BRCAness的概念被认为是由BRCA通路的遗传缺陷（包括BRCA1/2突变）引发的同源重组修复功能障碍。一定数量的胰腺导管腺癌（PDAC）患者有BRCAness。然而，尚未对PDAC中的BRCAness进行大规模分析。此外，没有基础研究检验BRCAness在PDAC细胞系中的意义。方法纳入92例手术治疗的PDAC患者。使用福尔马林固定和石蜡包埋的切除pdac标本，通过多重连接依赖探针扩增分析BRCAness。我们还使用集落形成试验分析了胰腺癌细胞系的BRCAness以及对顺铂和奥拉帕尼的敏感性。结果92例PDAC患者中，6例检测到brcaness阳性PDAC（6.5%）。brcaness阳性组和brcaness阴性组的总生存期和无进展生存期无显著差异。一种PDAC细胞系KP-2 BRCAness阳性，对顺铂和奥拉帕尼比BRCAness阴性细胞系更敏感。结论相当一部分PDAC的BRCAness阳性，提示BRCAness状态可作为晚期或复发PDAC选择抗癌治疗的有用生物标志物。
ObjectiveThe 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.MethodsNinety-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.ResultsOf 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.ConclusionsOur 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.
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影响因子：
8.8
作者：
Golan T;Sella T;O'Reilly EM;Katz MH;Epelbaum R;Kelsen DP;Borgida A;Maynard H;Kindler H;Friedmen E;Javle M;Gallinger S
通讯作者：
Gallinger S
影响因子：
11.5
作者：
Lips, Esther H.;Debipersad, Rashmie D.;Nederlof, Petra M.
通讯作者：
Nederlof, Petra M.
DOI：
10.1093/jnci/90.13.978
发表时间：
1998-07-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Abbott, DW;Freeman, ML;Holt, JT
通讯作者：
Holt, JT
影响因子：
45.3
作者：
Chen, Sining;Parmigiani, Giovanni
通讯作者：
Parmigiani, Giovanni
影响因子：
10.3
作者：
Thompson, D;Easton, DF
通讯作者：
Easton, DF