Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays.
Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays.
复制标题
DOI：
10.1186/1471-2407-14-786
复制
发表时间：
2014-10-28
期刊：
影响因子：
3.8
通讯作者：
Yamamoto N
中科院分区：
文献类型：
--
作者：
Kenmotsu H;Serizawa M;Koh Y;Isaka M;Takahashi T;Taira T;Ono A;Maniwa T;Takahashi S;Mori K;Endo M;Abe M;Hayashi I;Nakajima T;Ohde Y;Yamamoto N
尽管肺腺癌的治疗最近取得了相当大的进展，但在鳞状细胞肺癌的有效分子靶向治疗方面进展甚微。除了最近对鳞状细胞肺癌的全基因组特征进行了全面的研究外，对这种癌症进行基因分型也很重要。因此，我们进行了静冈肺癌突变研究，以分析胸部恶性肿瘤患者的驱动突变。在这里，我们报告的结果，基因分型的鳞状细胞肺癌患者。基于生物库系统，与临床和病理实验室合作，我们开发了一个基因分型面板，旨在评估10个基因中的24个突变（EGFR、KRAS、BRAF、PIK 3CA、NRAS、MEK 1、AKT 1、PTEN、HER 2和DDR2）、EGFR、MET、PIK 3CA、FGFR 1和FGFR 2拷贝数以及EML 4-ALK和ROS 1易位，使用焦磷酸测序加毛细管电泳，定量聚合酶链反应（PCR）和逆转录PCR。2011年7月至2012年11月期间，共有129例鳞状细胞肺癌和腺鳞癌患者入组本研究。我们在40%的病例中检测到了基因改变。基因改变包括：EGFR突变，6%; KRAS突变，4%; PIK 3CA突变，13%; NRAS突变，1%; KIF 5 b-RET融合基因，1%; EGFR拷贝数增加，5%; PIK 3CA拷贝数增加，15%;和FGFR 1拷贝数增加，5%。12例患者（9%）同时存在遗传改变。与福尔马林固定的石蜡包埋样本相比，在切除的快速冷冻样本中更频繁地检测到遗传变异（50%对29%）。此外，年龄≤70岁和从不吸烟的患者显示出高频率的遗传改变。这项研究是在亚洲鳞状细胞肺癌患者中进行的最大的前瞻性肿瘤基因分型研究之一。这些结果表明，将遗传分析纳入肺癌临床实践可能有助于鳞状细胞肺癌患者的个性化癌症治疗。本文的在线版本（doi：10.1186/1471-2407-14-786）包含补充材料，可供授权用户使用。
Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies. Here we report the results of genotyping in patients with squamous cell lung cancer. Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively. A total of 129 patients with squamous cell lung cancer and adenosquamous carcinoma were enrolled in this study between July 2011 and November 2012. We detected genetic alterations in 40% of all cases. Gene alterations included: EGFR mutations, 6%; KRAS mutations, 4%; PIK3CA mutations, 13%; NRAS mutations, 1%; KIF5b-RET fusion gene, 1%; EGFR copy number gain, 5%; PIK3CA copy number gain, 15%; and FGFR1 copy number gain, 5%. Twelve patients (9%) harbored simultaneous genetic alterations. Genetic alterations were detected more frequently in surgically-resected, snap-frozen samples than in formalin-fixed, paraffin-embedded samples (50% vs. 29%). In addition, patients aged ≤70 years old and never-smokers showed high frequencies of genetic alterations. This study represents one of the largest prospective tumor-genotyping studies to be performed in Asian patients with squamous cell lung cancer. These results suggest that incorporation of genetic profiling into lung cancer clinical practice may facilitate the administration of personalized cancer treatments in patients with squamous cell lung cancer. The online version of this article (doi:10.1186/1471-2407-14-786) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.1093/annonc/mdt205
发表时间：
2013-09
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Dearden S;Stevens J;Wu YL;Blowers D
通讯作者：
Blowers D
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
45.3
作者：
Scagliotti, Giorgio Vittorio;Parikh, Purvish;Gandara, David
通讯作者：
Gandara, David
影响因子：
11.5
作者：
Brooks, A. Nigel;Kilgour, Elaine;Smith, Paul D.
通讯作者：
Smith, Paul D.
影响因子：
5.3
作者：
Kawano, Osamu;Sasaki, Hidefumi;Fujii, Yoshitaka
通讯作者：
Fujii, Yoshitaka