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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.
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.
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.
Shares Matthew Meyerson, Somatic mutations from exome and genome sequencing (WXS, WGS), NF1 (neurofibromin), Broad Institute of MIT and Harvard.
Shares CREBBP, KMT2D, EP300, Somatic mutations from exome and genome sequencing (WXS, WGS).
Shares Nature Genetics, Non-small cell lung cancer (KEGG map), Driver mutation, Whole-exome & whole-genome sequencing.
Shares Matthew Meyerson, Broad Institute of MIT and Harvard, Driver mutation, RAS / RAF / MEK / ERK (MAPK).
Shares Nature Genetics, Driver mutation, Whole-exome & whole-genome sequencing, EGFR.
Shares Nature Genetics, Driver mutation, Whole-exome & whole-genome sequencing, TP53.
Shares Somatic mutations from exome and genome sequencing (WXS, WGS), SWI/SNF chromatin remodelling, Whole-exome & whole-genome sequencing, TP53.
Shares Nature Genetics, TP53, EGFR, KRAS.