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.
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.
Authors: Jonathan M Loree; Allan A L Pereira; Michael Lam; Alexandra N Willauer; Kanwal Raghav; Arvind Dasari; Van K Morris; Shailesh Advani; David G Menter; Cathy Eng; Kenna Shaw; Russell Broaddus; Mark J Routbort; Yusha Liu; Jeffrey S Morris; Rajyalakshmi Luthra; Funda Meric-Bernstam; Michael J Overman; Dipen Maru; Scott Kopetz Journal: Clin Cancer Res Date: 2017-11-27 Impact factor: 12.531
Authors: Humaid O Al-Shamsi; Jeremy Jones; Yazan Fahmawi; Ibrahim Dahbour; Aziz Tabash; Reham Abdel-Wahab; Ahmed O S Abousamra; Kenna R Shaw; Lianchun Xiao; Manal M Hassan; Benjamin R Kipp; Scott Kopetz; Amr S Soliman; Robert R McWilliams; Robert A Wolff Journal: J Gastrointest Oncol Date: 2016-12
Authors: Anthony W Tolcher; Razelle Kurzrock; Vincente Valero; Rene Gonzalez; Rebecca S Heist; Antoinette R Tan; Julie Means-Powell; Theresa L Werner; Carlos Becerra; Chenxi Wang; Cathrine Leonowens; Shanker Kalyana-Sundaram; Joseph F Kleha; Jennifer Gauvin; Anthony M D'Amelio; Catherine Ellis; Nageatte Ibrahim; Li Yan Journal: Cancer Chemother Pharmacol Date: 2020-02-15 Impact factor: 3.333