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

Source: https://onco.cc/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/  
OnCo record `paper-campbell-pan-lung-somatic-alterations-nat-genet-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Putting 660 lung adenocarcinomas and 484 squamous lung cancers side by side showed that squamous lung cancer has more in common with squamous cancers of other organs than with the adenocarcinoma growing next to it.

## Summary

Exome sequences and copy-number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumour-normal pairs were compared. Recurrent alterations in lung squamous carcinomas were more similar to those of other squamous carcinomas than to alterations in lung adenocarcinomas. Newly significantly mutated genes included PPP3CA, DOT1L and FTSJD1 in adenocarcinoma, RASA1 in squamous carcinoma, and KLF5, EP300 and CREBBP in both. New amplification peaks encompassed MIR21 in adenocarcinoma, MIR205 in squamous carcinoma and MAPK1 in both. Adenocarcinomas lacking receptor tyrosine kinase, RAS or RAF pathway alterations carried mutations in SOS1, VAV1, RASA1 and ARHGAP35. For neoantigens, 47% of adenocarcinomas and 53% of squamous carcinomas had at least five predicted neoepitopes.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Nature Genetics
- Year: 2016
- DOI: 10.1038/ng.3564
- Authors: Campbell JD, Alexandrov A, Kim J, et al.
- Findings: Squamous lung cancer resembles other squamous carcinomas more than it resembles lung adenocarcinoma.; New significantly mutated genes: RASA1 in squamous disease, KLF5, EP300 and CREBBP in both.; Adenocarcinomas without a receptor tyrosine kinase or RAS alteration carry mutations in RAS regulators instead.; Around half of tumours of each histology have five or more predicted neoepitopes.
- What it means: It is the empirical basis for treating the two histologies as separate diseases for targeted therapy and as one disease for immunotherapy, which is exactly how they are treated.
- Caveats: Exome and copy number only, so fusions and structural variants are underrepresented.; Neoepitope prediction is computational and does not establish that any of them is recognised.; Assembled from cohorts sequenced at different times with different pipelines.

## Sources

- Campbell et al., Nat Genet 2016: distinct patterns of somatic genome alteration in 660 lung adenocarcinomas and 484 squamous cell carcinomas: https://doi.org/10.1038/ng.3564
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27158780/
- cBioPortal study nsclc_tcga_broad_2016 (Pan-Lung TCGA and Broad, Nat Genet 2016; 1,144 tumour-normal pairs, 660 adenocarcinoma and 484 squamous): https://www.cbioportal.org/study/summary?id=nsclc_tcga_broad_2016

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [CREBBP](https://onco.cc/targets/crebbp/), [EGFR](https://onco.cc/targets/egfr/), [EP300](https://onco.cc/targets/ep300/), [KMT2D](https://onco.cc/targets/kmt2d/), [KRAS](https://onco.cc/targets/kras/), [NF1 (neurofibromin)](https://onco.cc/targets/nf1/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/)
- pathways: [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Neoantigen](https://onco.cc/terms/neoantigen/), [Somatic mutations from exome and genome sequencing (WXS, WGS)](https://onco.cc/terms/somatic-mutations-wxs-wgs/)
- people: [Matthew Meyerson](https://onco.cc/people/matthew-meyerson/)
- journals: [Nature Genetics](https://onco.cc/journals/nature-genetics/)

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