Mutational profiles of primary pulmonary adenocarcinoma and paired brain metastases disclose the importance of KRAS mutations.

Details

Serval ID
serval:BIB_128179CE8395
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutational profiles of primary pulmonary adenocarcinoma and paired brain metastases disclose the importance of KRAS mutations.
Journal
European journal of cancer
Author(s)
Vassella E., Kashani E., Zens P., Kündig A., Fung C., Scherz A., Herrmann E., Ermis E., Schmid R.A., Berezowska S.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
12/11/2021
Peer-reviewed
Oui
Volume
159
Pages
227-236
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Brain metastases present a significant complication in lung cancer with an unmet therapeutic need.
In this single-centre, retrospective study, we genotyped a clinico-pathologically well-annotated cohort of consecutively resected brain metastases of lung adenocarcinomas and paired primary tumours, diagnosed from 2000 to 2015, using the Ion Torrent Oncomine Comprehensive Cancer Panel v3.
Among 444 consecutive brain metastases, 210 (49%) originated from lung cancer. Analysis was successful in 111 samples, including 54 pairs of brain metastasis and primary tumour. Most driver alterations were preserved in brain metastases. Private alterations exclusive to primary tumours, brain metastases or both sites (intersecting cases) were present in 22%, 26% and 26% of cases, respectively. Seven percent had no shared mutations. KRAS mutations were more frequent in primary tumours metastasised to the brain (32/55, 58%) compared to TCGA (33%, p < 0.005) and own data from routine diagnostics, independent from clinical or pathological characteristics. Fourteen cases showed alterations in the EGFR signalling pathway including additional KRAS alterations that were private to brain metastases. KRAS G12C was detected most frequently (26% of patients) and KRAS G12C and G13C variants were significantly enriched in brain metastases. Synchronous and metachronous cases had a similar mutation profile.
Our results suggest an important role of KRAS alterations in the pathobiology of brain metastases from lung adenocarcinomas. This has direct therapeutic implications as inhibitors selectively targeting KRAS G12C are entering the clinics.
Keywords
Brain metastases, KRAS G12C, Lung cancer, NSCLC, Next generation sequencing
Pubmed
Open Access
Yes
Create date
17/11/2021 12:50
Last modification date
27/11/2021 6:37
Usage data