Somatic mutations affect key pathways in lung adenocarcinoma

@article{Ding2008SomaticMA,
  title={Somatic mutations affect key pathways in lung adenocarcinoma},
  author={Li Ding and Gad Getz and David A. Wheeler and Elaine R. Mardis and Michael D. McLellan and Kristian Cibulskis and Carrie Sougnez and Heidi Greulich and Donna M. Muzny and Margaret B. Morgan and Lucinda A. Fulton and Robert S. Fulton and Qunyuan Zhang and Michael C. Wendl and Michael S. Lawrence and David E. Larson and Ken Chen and David J. Dooling and Aniko Sabo and Alicia C. Hawes and Hua Shen and Shalini N. Jhangiani and Lora R. Lewis and Otis Hall and Yiming Zhu and Tittu Varghese Mathew and Yanru Ren and Jiqiang Yao and Steven E. Scherer and Kerstin Clerc and Ginger A. Metcalf and Brian Y. Ng and Aleksandar Milosavljevic and M L Gonzalez-Garay and John R. Osborne and Rick Meyer and Xiaoqi Shi and Yuzhu Tang and Daniel C. Koboldt and Ling Lin and Rachel M. Abbott and Tracie L. Miner and Craig S. Pohl and Ginger A. Fewell and Carrie A. Haipek and Heather K. Schmidt and Brian H. Dunford-Shore and Aldi T. Kraja and Seth D. Crosby and Christopher Sawyer and Tammi L. Vickery and Sacha N Sander and Jody S Robinson and Wendy Winckler and Jennifer Baldwin and Lucian R. Chirieac and Amit Dutt and Tim Fennell and Megan Hanna and Bruce E. Johnson and Roberto Onofrio and Roman K. Thomas and Giovanni Tonon and Barbara A. Weir and Xiaojun Zhao and Liuda Ziaugra and Michael C. Zody and Thomas J. Giordano and Mark B. Orringer and Jack A. Roth and Margaret R. Spitz and Ignacio I. Wistuba and Bradley A Ozenberger and Peter J. Good and Andrew C. Chang and David G. Beer and Mark A. Watson and Marc Ladanyi and Stephen R. Broderick and Akihiko Yoshizawa and William D. Travis and William Pao and Michael A. Province and George M. Weinstock and Harold Varmus and S. Gabriel and Eric S. Lander and Richard A. Gibbs and Matthew L Meyerson and Richard K. Wilson},
  journal={Nature},
  year={2008},
  volume={455},
  pages={1069-1075}
}
Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus… 
Comprehensive molecular profiling of lung adenocarcinoma
TLDR
High rates of somatic mutation were seen, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification, and MAPK and PI(3)K pathway activity was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation.
The transcriptional landscape and mutational profile of lung adenocarcinoma.
TLDR
The first large scale RNA sequencing study of lung adenocarcinoma is presented, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers.
Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer
TLDR
This study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
Diverse somatic mutation patterns and pathway alterations in human cancers
TLDR
This study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.
Diverse somatic mutation patterns and pathway alterations in human cancers.
TLDR
This study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.
Molecular biology of lung cancer.
Lung cancers are characterised by abundant genetic diversity with relatively few recurrent mutations occurring at high frequency. However, the genetic alterations often affect a common group of
Identification of somatic alterations in stage I lung adenocarcinomas by next‐generation sequencing
TLDR
Cell adhesion was the most enriched biological process in gene set analysis using the DAVID database and copy number amplification at 12q15, which includes MDM2, was identified as a recurrent somatic alteration in 4 of 10 tumors.
An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors
TLDR
The discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p, highlights the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.
Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1 and Hippo Pathway Genes
TLDR
It is shown that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumors without known driver mutations.
...
...

References

SHOWING 1-10 OF 60 REFERENCES
Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4
TLDR
This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas and suggests the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified.
Somatic mutations of the protein kinase gene family in human lung cancer.
TLDR
The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent.
Characterizing the cancer genome in lung adenocarcinoma
TLDR
A large-scale project to characterize copy-number alterations in primary lung adenocarcinomas using dense single nucleotide polymorphism arrays identifies 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 carcinomas.
p53: a frequent target for genetic abnormalities in lung cancer.
TLDR
These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.
Mutations of the BRAF gene in human cancer
TLDR
BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.
Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler.
TLDR
Genotyped Nras mutation status and Kras mutations in surgically treated lung adenocarcinoma cases and found 1 Nras gene mutation, a very rare event, in 195 patients, suggesting the mechanisms of Nras mutations for the sensitivity of molecular target therapy for lung cancer.
Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients
TLDR
Clinical and molecular characteristics of NSCLC, which harbour LKB1 mutations, are provided, including those with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma histologies.
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
TLDR
The sequence of well-annotated human protein-coding genes in two common tumor types is determined to define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.
Mutation analysis of the PTEN/MMAC1 gene in lung cancer
TLDR
The findings suggest that genetic abnormalities of the PTEN/MMAC1 gene are only involved in a relatively small subset of lung cancers.
...
...