Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
Access Status
Authors
Date
2014Type
Metadata
Show full item recordCitation
Source Title
ISSN
School
Remarks
This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by-nc-sa/3.0/
Collection
Abstract
Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
Related items
Showing items related by title, author, creator and subject.
-
Ye, L.; Leslie, C.; Jacques, Angela; Mesbah Ardakani, N.; Amanuel, B.; Millward, M. (2018)© 2018, United States & Canadian Academy of Pathology. Immune checkpoint inhibition is an important therapeutic option in patients with non-small cell lung cancer. Programmed cell death ligand-1 (PD-L1) expression may ...
-
Edling, C.; Selvaggi, F.; Buus, R.; Maffucci, T.; Di Sebastiano, P.; Friess, H.; Innocenti, P.; Kocher, H.; Falasca, Marco (2010)Purpose: Phosphoinositide 3-kinase (PI3K) signaling is well established as important in cancer. To date most studies have been focused on the PI3K/p110a isoform, which has been found to be mutated in several different ...
-
Abrams, S.; Lertpiriyapong, K.; Yang, L.; Martelli, A.; Cocco, L.; Ratti, S.; Falasca, Marco; Murata, R.; Rosalen, P.; Lombardi, P.; Libra, M.; Candido, S.; Montalto, G.; Cervello, M.; Steelman, L.; McCubrey, J. (2018)Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5–10%. Mutations at ...