ArticleThe oncologist2024
Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations.
Article in The oncologist, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Application of Systems Genetics to Investigate Molecular Pathology of Early-Onset Colorectal Cancer.Chemical biology & drug design · 2026Review
- Mutations of Kinases and GTPases in Cancers.Cancers · 2026Article
- Co-Occurrence of Nuclear-Catenin and H3K27me3 Expression in Advanced Colorectal Cancer: A Retrospective Observational Study.Current oncology (Toronto, Ont.) · 2026Observational
- From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer.Molecular diagnosis & therapy · 2026Review
- Enhanced computational strategies for categorizing HER2 kinase domain variants of uncertain significance through structural and functional analysis.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- UnveilingTranslational cancer research · 2025Article
- Review
- The role of PIK3CA gene mutations in colorectal cancer and the selection of treatment strategies.Frontiers in pharmacology · 2024Review
- Using Tumor-Informed Circulating Tumor DNA (ctDNA)-Based Testing for Patients with Anal Squamous Cell Carcinoma.The oncologist · 2023Article
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Authors and funding
12 authors.
Funding
Abstract
introductionApproximately 20% of patients living with colorectal cancer (CRC) have activating mutations in their tumors in the PIK3CA oncogene. Two or more activating mutations (multi-hit) for the PIK3CA allele increase PI3K⍺ signaling compared to single-point mutations, resulting in exceptional response to PI3K⍺ inhibition. We aimed to identify the prevalence of PIK3CA multi-hit mutations in metastatic CRC to identify patients who may benefit from PI3K inhibitors.
methodsThe Foundation Medicine database (Boston, MA, USA) was analyzed for patients with CRC who underwent genomic profiling on tumor DNA isolated during routine clinical care from 2013 to 2021. Molecular and clinical variables were abstracted for patients with PIK3CA mutations.
resultsWe identified 49 051 patients with CRC who underwent Foundation Medicine testing. 710/41154 (1.7%) patients had multi-hit PIK3CA mutations, of which 53% were male (n = 448) with a median age of 60. Microsatellite status was available for 697 patients with multi-hit PIK3CA and 17.6% (123/697) were microsatellite instability-high. Clinically relevant mutations in KRAS and BRAFV600E were seen in 459/710 (64.7%) and 65/710 (9.1%), respectively. The 4 most common PIK3CA variants were H1047R (9.8%), E545K (9.2%), E542K (9.0%), and R88Q (7.1%). The most common variant pair was E542K-E545K (4.7%).
conclusionsMulti-hit mutations in PIK3CA are seen in 1.7% of advanced CRC, a meaningful prevalence given the high burden of CRC worldwide, and may represent a subset of patients that have enhanced sensitivity to PI3K inhibition. Future investigation regarding the clinical utility of PI3K inhibitors is warranted in multi-hit PIK3CA CRC.
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