新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » BIOON报道 » Cancer:研究发现子宫颈癌不同亚型之间的基因差异

Cancer:研究发现子宫颈癌不同亚型之间的基因差异

来源:生物谷 2013-08-25 10:20

2013年8月24日讯 /生物谷BIOON/--一项新的研究发现宫颈癌最常见两种类型(腺癌和鳞状细胞癌)的基因组存在差异,提示患者可能受益于针对不同类型的分子特质疗法。

该研究发表在8月23日的Cancer杂志上,由Dana-Farber癌症研究所和Brigham and Women医院(BWH)研究人员完成,首次比较了两个子宫颈癌亚型(腺癌和鳞状细胞癌)的癌症相关基因突变谱。

在对80例肿瘤样本测试中,研究人员发现了两个基因的突变率很高:PIK3CA和KRAS。PIK3CA突变在这两个亚型中都被发现,而KRAS突变只在腺癌中发现。

将他们的研究结果与患者的治疗和生存的数据联系起来分析,研究人员发现,PIK3CA突变与较短的生存期相关,这些PIK3CA突变肿瘤患者诊断后中位生存期为67个月,而缺乏PIK3CA突变的患者中位生存期为90个月。

研究结果表明,部分患者虽然疾病死亡风险较高,但可能将更多受益于有针对性的治疗方法。在宫颈肿瘤样本中PIK3CA突变率很高的患者,提示将受益于PI3激酶抑制剂药物。腺癌患者可能受益于MEK抑制剂。

虽然子宫颈抹片检查有助于降低鳞状细胞子宫颈癌的发病率,每年全世界275,000人死于子宫颈癌,宫颈癌是癌症死亡的第二大原因。

在研究中,研究者探测80例宫颈癌(40腺癌和40鳞状细胞癌)肿瘤患者的DNA,1200个与癌症有关的基因突变。他们发现,31%的样本有PIK3CA突变,17.5%的腺癌(鳞状细胞癌没有一例)有KRAS突变,以及7.5%的鳞状细胞癌(腺癌没有一例)有一个罕见的EGFR基因突变。

虽然目前的治疗策略并没有考虑宫颈肿瘤是否是腺癌还是鳞状细胞癌,但研究表明,识别和针对不同患者亚群开展治疗可改善早期或晚期疾病患者的治疗结果。(生物谷Bioon.com)

Oncogenic mutations in cervical cancer

Alexi A. Wright, Brooke E. Howitt, Andrea P. Myers, Suzanne E. Dahlberg, Emanuele Palescandolo, Paul Van Hummelen, Laura E. MacConaill, Melina Shoni, Nikhil Wagle, Robert T. Jones, Charles M. Quick, Anna Laury, Ingrid T. Katz, William C. Hahn, Ursula A. Matulonis, Michelle S. Hirsch.

BACKGROUND
Cervical cancer is the second leading cause of cancer deaths among women worldwide. The objective of this study was to describe the most common oncogenic mutations in cervical cancers and to explore genomic differences between the 2 most common histologic subtypes: adenocarcinoma and squamous cell carcinoma.

METHODS
A high-throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry-based genotyping platform and were validated using orthogonal chemistry. Epidermal growth factor receptor (EGFR) mutations were further validated by massive parallel sequencing. Human papilloma virus (HPV) genotyping also was performed.

RESULTS
Validated mutations were detected in 48 of 80 tumors (60%) examined. The highest mutation rates were in the genes phosphatidylinositol 3-kinase, catalytic subunit α (PIK3CA) (31.3%); Kirsten rat sarcoma viral oncogene homolog (KRAS) (8.8%); and EGFR (3.8%). PIK3CA mutation rates did not differ significantly between adenocarcinomas and squamous cell carcinomas (25% vs 37.5%, respectively; P=.33). In contrast, KRAS mutations were identified only in adenocarcinomas (17.5% vs 0%; P?=?.01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs 7.5%; P?=?.24). There were no associations between HPV-16 or HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival (67.1 months vs 90.3 months; hazard ratio, 9.1; 95% confidence interval, 2.8-29.5 months; P<.001).

CONCLUSIONS
Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3K and MEK inhibitors.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库