Mutational landscape of pan-cancer patients with PIK3CA alterations in Chinese population View Full Text


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Article Info

DATE

2022-07-01

AUTHORS

Qingfeng Huang, Yang Zhou, Bowen Wang, Yi Zhao, Fengxia Zhang, Bowen Ding

ABSTRACT

PurposeTo analyze the mutational landscape of pan-cancer patients with PIK3CA mutations in Chinese population in real-world.MethodsWe analyzed PIK3CA mutation status in sequencing data of cell-free DNA from plasma and genomic DNA from matched peripheral blood lymphocyte in 11,904 Chinese pan-cancer patients, and compared them with genomic data from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Besides, concomitant genomic aberrations in PIK3CA-mutated samples were detected to investigate cancer driver genes, as well as their enriched pathways. Meanwhile, the mutations of Alpelisib targeting genes were screened and their co-alterations were analyzed according to OncoKB definition to identify the potential actionable ones.ResultsThe proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The most common PIK3CA mutation hotspots were found to be E545K, E542K and H1047R. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. Compared with COSMIC cohort, the mutation frequencies of Alpelisib-targeted genes in breast cancer were significantly reduced in the Chinese cohort. All PIK3CA-mutated patients had concomitant genomic aberrations. While the most common concomitant genomic alterations occurred in TP53, EGFR and FAT1, these co-mutated genes were mainly enriched in RTK/RAS pathway, PI3K pathway and P53 pathway. Moreover, 83.6% of patients carrying mutations in Alpelisib-targeted genes had at least one actionable concomitant alteration. Level 1 actionable alteration was identified in LUAD, BRCA, COAD, LUSC, READ, and STAD.ConclusionCompared with the Western cohort, the mutation frequency of PIK3CA in breast cancer was reduced in the Chinese cohort. RTK/RAS pathway, PI3K pathway and P53 pathway were identified as the most common co-mutation pathways, suggesting that they may potentially serve as targets for possible Alpelisib-based combination therapy. More... »

PAGES

146

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12920-022-01297-7

DOI

http://dx.doi.org/10.1186/s12920-022-01297-7

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https://app.dimensions.ai/details/publication/pub.1149161639

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35778737


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