Characterizing the cancer genome in lung adenocarcinoma

By B. Weir, M. S. Woo, Gad Getz, S. Perner, Li Ding, Rameen Beroukhim, William M. Lin, M. Province, A. Kraja, L. Johnson and 60 more. Nature, 2007

1,146 citations recorded by the source corpus.

Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development of high-resolution, genome-wide approaches are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours (n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in ∼12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0d62b33e418900bad0de7888ce10c0c6c13c67b8

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Citations in the corpus

GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers (2011, methodology): “GISTIC has been applied to multiple cancer types, including glioblastoma [10,15], lung adenocarcinoma [16], melanoma [17], colorectal carcinoma [18], hepatocellular carcinoma [19], ovarian carcinoma [20], medulloblastoma [21], and lung and esophageal squamous carcinoma [22], and has helped identify ”
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The somatic genomic landscape of chromophobe renal cell carcinoma (2014, background): “…represents a mechanism for increased TERT expression in cancer different from point mutations observed in a wide variety of cancers (Heidenreich et al., 2014; Huang et al., 2013), gene amplification (Weir et al., 2007; Chudnovsky et al., 2005), and germline polymorphisms (Rafnar et al., 2009).”
Identification of DOK family genes as lung tumor suppressors (2010, neutral): “3, one of the regions most frequently deleted in human lung cance”
The landscape of somatic copy-number alteration across human cancers (2010, background): “In some cases, focal SCNAs have led to the identification of cancer-causing genes and suggested specific therapeutic approaches 7–14 .”
A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. (2009, background): “K-ras amplification is observed in lung and pancreatic tumor specimens (Aguirre et al., 2004; Weir et al., 2007), and might provide a useful biomarker of response to therapeutics that target K-Ras-addicted human cancers.”
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SOX2 Is an Amplified Lineage Survival Oncogene in Lung and Esophageal Squamous Cell Carcinomas (2009, methodology): “Data were analyzed using GISTIC (Genomic Identification of Significant Targets in Cancer”
Proteogenomic characterization reveals therapeutic vulnerabilities in lung adenocarcinoma (2020, result): “0/ GISTIC_2_0_23.tar.gz iProFun (Song et al., 2019) https://github.com/WangLab-MSSM/ iProFun ESTIMATE (Yoshihara et al., 2013) https://bioinformatics.mdanderson.org/ public-software/estimate/ WebGestaltR (Wang et al., 2017) http://www.webgestalt.org/ Joint Random Forest (Petralia et al., 2016) https”
Integrative genomic profiling of human prostate cancer (2010, background): “These data clarify the role cate several new ones, and provide a blueprint for clinical dev into the molecular classification of cancers and have the potential to identify new therapeutic targets (Cancer Genome Atlas Research Network, 2008; Ding et al., 2008; Jones et al., 2008; Parsons et al., 2008”