Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing

By Marcin Imielinski, A. Berger, P. Hammerman, Bryan Hernandez, Trevor J Pugh, Eran Hodis, Jeonghee Cho, J. Suh, M. Capelletti, A. Sivachenko and 35 more. Cell, 2012

1,811 citations recorded by the source corpus.

SUMMARY Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for over 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole genome sequence analysis revealed frequent structural re-arrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.

Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/fcc794d59b6567b127253557b5b02bda2e201484

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Citations in the corpus

Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity (2013, background): “Compared to other cancer types, this overall mutation frequency is high and exceeded only by lung cancer 17,18 and melanoma 19 , diseases that emerge from clear mutagens.”
STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma (2018, neutral): “KL KP K-only 54(0) 56(0) 64(0) 25(5) 36(2) 45(4) 10(12) 19(14) 27(18) 4(16) 4(26) 4(34) 2(17) 1(29) 1(37) 1(18) 1(29) 1(37) 1(18) 1(29) 1(37) 0(19) 1(29) 0(38) 0(19) 0(30) 0(38) KL KRASSTK11”
Co-occurring genomic alterations define major subsets of KRAS - mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities (2015, neutral): “In contrast, KEAP1 mutations were infrequently observed among KP tumors in either the TCGA or BATTLE-2 cohorts, as well as in a separate collection of 49 surgically resected KRAS-mutant lung adenocarcinomas reported previously (18), unless the tumor also harbored an STK11/LKB1 mutation (i.”
Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors (2013, background): “To broaden our findings that Pd-l1/2 expression is upregulated in response to EGFR driven oncogenic signals in mice, we compared PD-L1 ( CD274 ) and PD-L2 ( PDCD1LG2 ) expression in patient-derived established NSCLC cell lines (23), with a particular focus on lines with EGFR and KRAS mutations.”
Discovery and saturation analysis of cancer genes across 21 tumor types (2014, methodology): “We ask: (1) Can large-scale genomic analysis across tumor types reliably identify all known cancer genes? (2) Will it reveal many new candidate cancer genes? (3) How far do we stand from having a complete catalog of cancer genes – at least those of intermediate frequency? We used rigorous statistica”
Pathway and Network Analysis of Cancer Genomes (2015, neutral): “Recent studies have painted a portrait of the mutation landscape for multiple cancers 2 including pancreatic 3 , lung 4 , breast 5 , brain 6 , and ovarian 7 .”
The Somatic Genomic Landscape of Glioblastoma (2013, background): “, 2013), lung adenocarcinoma (Imielinski et al., 2012), and melanoma (Berger et al.”