小柯机器人

美国国家癌症研究所Maria Teresa Landi小组揭示从不吸烟者肺癌的基因组和进化分类。这一研究成果发表在2021年9月6日出版的国际学术期刊《自然—遗传学》上。

研究人员对232个从不吸烟者的肺癌（LCINS）进行了高覆盖率的全基因组测序，并发现了由拷贝数畸变定义的3个亚型。优势亚型（piano），在吸烟者的肺癌中很少见，具有体细胞UBA1突变、生殖系AR变异和干细胞样特性，包括低突变负荷、高瘤内异质性、长端粒、频繁的KRAS突变和缓慢生长，这是由肿瘤诊断前多年出现的癌症驱动者祖细胞所表明的。其他亚型的特点是特定的扩增和EGFR突变（Mezzo-forte）和全基因组加倍（forte）。

强烈的吸烟特征没有被检测到，甚至在暴露于二手烟的病例中也是如此。受体酪氨酸激酶-Ras通路内的基因对生存有不同的影响；五个基因组的改变使死亡率独立翻倍。这些发现为LCINS的个性化治疗提供了途径。

据悉，LCINS是癌症死亡的一个常见原因，但其基因组图谱特征不明显。

附：英文原文

Title: Genomic and evolutionary classification of lung cancer in never smokers

Author: Zhang, Tongwu, Joubert, Philippe, Ansari-Pour, Naser, Zhao, Wei, Hoang, Phuc H., Lokanga, Rachel, Moye, Aaron L., Rosenbaum, Jennifer, Gonzalez-Perez, Abel, Martnez-Jimnez, Francisco, Castro, Andrea, Muscarella, Lucia Anna, Hofman, Paul, Consonni, Dario, Pesatori, Angela C., Kebede, Michael, Li, Mengying, Gould Rothberg, Bonnie E., Peneva, Iliana, Schabath, Matthew B., Poeta, Maria Luana, Costantini, Manuela, Hirsch, Daniela, Heselmeyer-Haddad, Kerstin, Hutchinson, Amy, Olanich, Mary, Lawrence, Scott M., Lenz, Petra, Duggan, Maire, Bhawsar, Praphulla M. S., Sang, Jian, Kim, Jung, Mendoza, Laura, Saini, Natalie, Klimczak, Leszek J., Islam, S. M. Ashiqul, Otlu, Burcak, Khandekar, Azhar, Cole, Nathan, Stewart, Douglas R., Choi, Jiyeon, Brown, Kevin M., Caporaso, Neil E., Wilson, Samuel H., Pommier, Yves, Lan, Qing, Rothman, Nathaniel, Almeida, Jonas S., Carter, Hannah, Ried, Thomas, Kim, Carla F., Lopez-Bigas, Nuria, Garcia-Closas, Montserrat, Shi, Jianxin, Boss, Yohan, Zhu, Bin, Gordenin, Dmitry A., Alexandrov, Ludmil B., Chanock, Stephen J., Wedge, David C., Landi, Maria Teresa

Issue&Volume: 2021-09-06

Abstract: Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers’ progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase–Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.

DOI: 10.1038/s41588-021-00920-0

Source: https://www.nature.com/articles/s41588-021-00920-0

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex