IRS2
Overview
IRS2 (Insulin Receptor Substrate 2) encodes a cytoplasmic signaling adapter that mediates insulin and IGF receptor signaling through PI3K/AKT and RAS/MAPK pathways. In colorectal cancer, IRS2 shows overexpression on chromosome 13 that is mutually exclusive with IGF2 overexpression and PI3K pathway mutations, suggesting it represents an alternative mechanism of IGF/PI3K pathway activation.
Alterations observed in the corpus
- Overexpression on chromosome 13 identified in TCGA colorectal adenocarcinoma cohort (276 tumors); mutually exclusive with IGF2 overexpression and PI3K pathway mutations PMID:22810696
- Recurrent focal amplification in SCLC; identified among genes with recurrent copy number gains in the SCLC genomic landscape PMID:26168399
Cancer types (linked)
- COADREAD (colorectal adenocarcinoma): Copy-number-driven overexpression on chr13; mutually exclusive with IGF2 amplification and PI3K pathway events, indicating convergent pathway activation PMID:22810696
Co-occurrence and mutual exclusivity
- Mutually exclusive with IGF2 overexpression and PIK3CA/PIK3R1/PTEN alterations in colorectal adenocarcinoma, supporting a shared downstream PI3K/IGF signaling node PMID:22810696
Therapeutic relevance
- IRS2 overexpression as an alternative PI3K pathway activation mechanism may have implications for IGF1R or PI3K inhibitor sensitivity in colorectal cancer.
Open questions
- Whether IRS2 overexpression is driven by focal amplification at 13q or a broader chromosomal gain has not been fully resolved.
- Clinical significance of IRS2 overexpression vs. IGF2 amplification for therapeutic response to IGF1R-targeted agents requires prospective evaluation.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:26168399
This page was processed by crosslinker on 2026-05-14.