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Comprehensive genomic characterization of head and neck squamous cell carcinomas

机译：头颈部鳞状细胞癌的综合基因组学表征

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摘要

本期封面为挪威艺术家Espen Kluge的作品"Perception"，它是"由很多线条构成的一张脸"。轔状细胞头预癌是最常见和最致命的癌症之一。尽管对手术、放疗和化疗组合治疗最初有反应，但所有肿瘤中大约一半在最初诊断之后两年内通常会复发。分子标记和定向治疗迄今对这种病几乎没有任何效果。在这篇论文中，"癌症基因组图谱"研究团队发表了整个基因组内所发生改变的详细情况，揭示了对具有不同"人乳头瘤病毒"(HPA)状态的"头颈鳞状细胞癌"(HNSCCs)有潜在生物和临床意义的关键遗传事件。EGFR、FGFRs、 PIK3CA和"依赖于细胞周期蛋白的激酶"所发生的突变，代表着在绝大多数HNSCCs中进行治疗干预的候选目标。%The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
机译：本期封面为挪威艺术家Espen Kluge的作品"Perception"，它是"由很多线条构成的一张脸"。辚状细胞头预癌是最常见和最致命的癌症之一。尽管对手术、放疗和化疗组合治疗最初有反应，但所有肿瘤中大约一半在最初诊断之后两年内通常会复发。分子标记和定向治疗迄今对这种病几乎没有任何效果。在这篇论文中，"癌症基因组图谱"研究团队发表了整个基因组内所发生改变的详细情况，揭示了对具有不同"人乳头瘤病毒"(HPA)状态的"头颈鳞状细胞癌"(HNSCCs )有潜在生物和临床意义的关键遗传事件。 EGFR、FGFRs、 PIK3CA和"依赖于细胞周期蛋白的激酶"所发生的突变，代表着在绝大多数HNSCCs中进行治疗干预的候选目标。 %The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tu mours. Therapeutic candidate alterations were identified in most HNSCCs.

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  • 来源
    《Nature》 |2015年第7536期|576-582a2|共8页
  • 作者

    Michael S. Lawrence; Carrie Sougnez; Lee Lichtenstein; Kristian Cibulskis; Eric Lander; et al;

  • 作者单位

    The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

    The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

    The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

    The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

    The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

    The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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