Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas

By Joshua D. Campbell, A. Alexandrov, Jaegil Kim, J. Wala, A. Berger, C. Pedamallu, S. Shukla, Guangwu Guo, Angela N. Brooks, Bradley A. Murray and 124 more. Nature Genetics, 2016

1,096 citations recorded by the source corpus.

To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor–normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase–Ras–Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.

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

View Paper: https://www.semanticscholar.org/paper/6f703fac33264a37b860ff5019776137a0dac2f9

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Citations in the corpus

Genomic and Functional Approaches to Understanding Cancer Aneuploidy (2018, background): “In contrast, in lung adenocarcinoma, less than half of tumors had 3p loss and only 13% had 3q gain (Campbell et al., 2016), and these did not significantly co-occur (p = 0.”
Fully-Connected Neural Networks with Reduced Parameterization for Predicting Histological Types of Lung Cancer from Somatic Mutations (2020, methodology): “For example, among somatic mutation sites showing top 10 negative PC scores (Table 5b), KRAS, EGFR, STK11, and SETD2 have already been shown to be significantly mutated genes for LUAD, and, more importantly, the majority of these genes seem to be mutated exclusively in LUAD and not in LUSC [22].”
Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution (2017, methodology): “To further validate our findings in a larger cohort with RNAseq data, we obtained 383 lung adenocarcinomas and 309 lung squamous-cell carcinomas samples from TCGA (Campbell et al., 2016).”
Comprehensive Analysis of Hypermutation in Human Cancer (2017, positive): “This observation was previously reported for three hypermutant lung squamous cell carcinomas (Campbell et al., 2016).”
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer (2017, background): “Of note, the median number of somatic mutations found in the pan-lung cancer analysis of TCGA data was 261, and 327 in a separate study of metastatic lung cancers (18,25).”
AACR Project GENIE: Powering Precision Medicine through an International Consortium (2017, background): “Finally, GENIE data exhibit similar patterns of mutual exclusivity observed in TCGA.”
Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. (2018, background): “…in NSCLC comprising 11%–16%of lung adenocar- 578 Cell 172, 578–589, January 25, 2018 ª 2018 Elsevier Inc. cinomas (45%–50%ofmutantKRAS is p.G12C) (Campbell et al., 2016; Jordan et al., 2017), as well as 1%–4% of pancreatic and colorectal adenocarcinomas, respectively (Bailey et al., 2016;…”
Genomic features of response to combination immunotherapy in patients with advanced non-small cell lung cancer (2018, result): “Notably, TP53mutations were also associated with increased mutation burden in both the cohort of combination immunotherapy NSCLCs and TCGA NSCLCs (Figures S3C–S3F and Table S4).”
Oncogenic Signaling Pathways in The Cancer Genome Atlas (2018, background): “Speciﬁc germline mutations in this gene are involved in Noonan syndrome (Lepri et al., 2011), and recurrent somatic mutations in SOS1 were recently identiﬁed in otherwise RAS-pathway driver-negative lung adenocarcinoma samples (Campbell et al., 2016).”