Comprehensive genomic characterization of squamous cell lung cancers

By P. Hammerman, D. Voet, M. Lawrence, R. Jing, Kristian Cibulskis, A. Sivachenko, P. Stojanov, A. McKenna, Eric S. Lander, Stacey Gabriel and 320 more. Nature, 2012

3,784 citations recorded by the source corpus.

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Subfields: Cancer Research, Plant Science, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/7abf79103497ea2cac1a0b4fc484d30649d3d1ad

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Balázs Győrffy
2. Gad Getz
3. A. Lánczky
4. Eric S. Lander
5. Matthew Meyerson
6. Kristian Cibulskis
7. M. Lawrence
8. Christopher Sander

In Plant Science

1. P. Park
2. Christopher Sander
3. Javier Herrero
4. Haiyuan Yu
5. Kathryn M Beal
6. David Haussler
7. Marco A. Marra
8. Jacqueline E. Schein

In Pulmonary and Respiratory Medicine

1. Balázs Győrffy
2. A. Lánczky
3. Mark A. Rubin
4. B. Gan
5. Zhuang Li
6. Timothy Triche
7. Furong Zeng
8. Yu Meng

Citations in the corpus

• Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer (2013, background): “A pre-requisite for the reproducibility of such genomic signatures is the availability of raw data, which was only ensured by publications of the last six years [9,10,11,12,13,14,15,16,17,18].”
• Comprehensive Molecular Characterization of Urothelial Bladder Carcinoma (2014, background): “Reuter(23), Oregon Health and Science University, Department of Urology - Theresa Koppie(24), University of North Carolina, Lineberger Cancer Center - Lori Boice(25), Wendy Kimryn Rathmell(25), Leigh Thorne(25), University of Pittsburgh - Sheldon Bastacky(26), Benjamin Davies(26), Rajiv Dhir(26), Je”
• Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics (2013, background): “In light of these studies and the growing availability of whole-genome cancer sequencing (13-20), an integrated framework facilitating functional interpretation of noncoding variants would be useful.”