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同源重组修复基因突变与胰腺癌对奥沙利铂反应之间的关联

Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer.

作者信息

Kondo Tomohiro, Kanai Masashi, Kou Tadayuki, Sakuma Tomohiro, Mochizuki Hiroaki, Kamada Mayumi, Nakatsui Masahiko, Uza Norimitsu, Kodama Yuzo, Masui Toshihiko, Takaori Kyoichi, Matsumoto Shigemi, Miyake Hidehiko, Okuno Yasushi, Muto Manabu

机构信息

Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Biomedical Department, Mitsui Knowledge Industry Co., Ltd., Tokyo, Japan.

出版信息

Oncotarget. 2018 Apr 13;9(28):19817-19825. doi: 10.18632/oncotarget.24865.

Abstract

OBJECTIVES

We aimed to examine the association between homologous recombination repair (HRR)-related gene mutations and efficacy of oxaliplatin-based chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).

RESULTS

Non-synonymous mutations in HRR-related genes were found in 13 patients and only one patient had a family history of pancreatic cancer. Eight patients with HRR-related gene mutations (group A) and nine without HRR-related gene mutations (group B) received oxaliplatin-based chemotherapy. Median progression-free survival after initiation of oxaliplatin-based chemotherapy was significantly longer in group A than in group B (20.8 months vs 1.7 months, = 0.049). Interestingly, two patients with inactivating HRR-related gene mutations who received FOLFIRINOX as first-line treatment showed exceptional responses with respect to progression-free survival for > 24 months.

MATERIALS AND METHODS

Complete coding exons of 12 HRR-related genes ( and ) were sequenced using a Clinical Laboratory Improvement Amendment-certified multiplex next-generation sequencing assay. Thirty consecutive PDAC patients who underwent this assay between April 2015 and July 2017 were included.

CONCLUSIONS

Our results suggest that inactivating HRR-related gene mutations are predictive of response to oxaliplatin-based chemotherapy in patients with PDAC.

摘要

目的

我们旨在研究同源重组修复(HRR)相关基因突变与胰腺导管腺癌(PDAC)患者基于奥沙利铂的化疗疗效之间的关联。

结果

在13例患者中发现了HRR相关基因的非同义突变,只有1例患者有胰腺癌家族史。8例有HRR相关基因突变的患者(A组)和9例无HRR相关基因突变的患者(B组)接受了基于奥沙利铂的化疗。A组基于奥沙利铂的化疗开始后的中位无进展生存期明显长于B组(20.8个月对1.7个月,P = 0.049)。有趣的是,2例接受FOLFIRINOX作为一线治疗的有失活HRR相关基因突变的患者在无进展生存期方面表现出超过24个月的异常反应。

材料与方法

使用经临床实验室改进修正案认证的多重下一代测序分析对12个HRR相关基因(和)的完整编码外显子进行测序。纳入了2015年4月至2017年7月间接受该分析的30例连续PDAC患者。

结论

我们的结果表明,失活的HRR相关基因突变可预测PDAC患者对基于奥沙利铂的化疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ca/5929428/fefe5e4f8ba0/oncotarget-09-19817-g001.jpg

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