11月30日,，PLoS ONE在線發(fā)表了中科院上海生科院生化與細胞所季紅斌研究組與復(fù)旦大學(xué)腫瘤醫(yī)院合作的研究成果 ,該工作在更大樣本的基礎(chǔ)上進一步建立并完善了非吸煙肺腺癌人群中關(guān)鍵的致癌基因突變譜。
季紅斌課題組長期致力于肺癌基因組學(xué)的研究,。以往在52例肺癌樣本中的研究結(jié)果表明非吸煙肺腺癌患者來源的腫瘤樣本具有特殊的致癌基因突變譜：約90%患者的腫瘤樣本中具有EGFR, KRAS, HER2及EML4-ALK四種基因突變中的一種。由于目前臨床上已經(jīng)有一些小分子藥物可以有效地抑制突變的EGFR,、HER2和ALK的活性,，因此絕大多數(shù)非吸煙的肺腺癌患者有可能從這些藥物的治療中獲益的。
最近季紅斌研究組在前期工作基礎(chǔ)上進行了更大規(guī)模和更為深入的分析：在202例非吸煙肺腺癌患者來源的腫瘤樣本中,，對EGFR, KRAS, HER2, ALK突變以及最近發(fā)現(xiàn)的ROS1基因融合進行了檢測以及臨床相關(guān)性分析,。研究結(jié)果表明，大約89%患者的腫瘤樣本中具有而且只具有以上五種突變中的一種,。這一工作不但證實了該課題組以往的研究結(jié)果,，而且發(fā)現(xiàn)EGFR突變的患者與非EGFR突變的患者相比年齡偏大(58.3 Vs 54.3, P = 0.016)，而存在未知基因突變的患者與具有已知突變的患者相比年齡偏小 (52.3 Vs 57.9, P = 0.013),。該研究將為臨床的個體化分子靶向治療提供理論依據(jù),。(生物谷Bioon.com)
doi:10.1371/journal.pone.0028204
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Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers
Chenguang Li, Rong Fang, Yihua Sun, Xiangkun Han, Fei Li, Bin Gao, A. John Iafrate, Xin-Yuan Liu, William Pao, Haiquan Chen, Hongbin Ji
We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations.We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing.152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5′ partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected.The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor.
