Mutations in the RAS and PI3K pathways are associated with metastatic location in colorectal cancers

Yuan Tzu Lan, Lin Jen-Kou, Chien Hsing Lin, Shung Haur Yang, Chun Chi Lin, Huann Sheng Wang, Wei Shone Chen, Tzu Chen Lin, Jeng Kai Jiang*, Shih Ching Chang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Background and objectives Identification of mutations in the downstream epidermal growth factor receptor (EGFR) signaling pathway could provide important insights of EGFR-targeted therapies in colorectal cancers. We analyzed the mutation spectra of the PI3K/PTEN/AKT and RAS/RAF/MAPK pathways in colorectal cancers and the associations of these mutations with sites of metastases or recurrence. Methods The study population comprised 1,492 retrospectively collected stages I-IV colorectal cancer specimens. Tissue was obtained between 2000 and 2010 at a single hospital. We analyzed 61 hot spots using MALDI-TOF mass spectrometry for nucleic acid analysis. Results Mutations were found in the RAS pathway in 47.3% of patients and in the PI3K pathway in 14.3% of patients, with 9.2% of patients carrying mutations in both pathways. Both the RAS and PI3K pathway mutations were significantly associated with proximal tumors, mucinous tumors, and microsatellite instability. Tumors carrying a RAS pathway mutation exhibited a higher frequency of lung and peritoneal metastasis than did tumors with a wild-type gene (P=0.025 and 0.009, respectively). NRAS gene mutation was significantly associated with lung metastasis (P=0.001). Conclusions Somatic mutations in the RAS pathway of the primary tumor in colorectal cancer can influence patterns of metastasis and recurrence.

Original languageEnglish
Pages (from-to)905-910
Number of pages6
JournalJournal of Surgical Oncology
Issue number7
StatePublished - 1 Jun 2015


  • colorectal cancer
  • epidermal growth factor receptor
  • metastasis
  • signaling pathway


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