SOS1 mutations are rare in human malignancies: Implications for Noonan syndrome patients

Kenneth D. Swanson, Jordan M. Winter, Marcelo Reis, Mohamed Bentires-Alj, Heidi Greulich, Rupinder Grewal, Ralph H. Hruban, Charles J. Yeo, Yosuf Yassin, Oleg Iartchouk, Kate Montgomery, Susan P. Whitman, Michael A. Caligiuri, Mignon L. Loh, D. Gary Gilliland, A. Thomas Look, Raju Kucherlapati, Scott E. Kern, Matthew Meyerson, Benjamin G. Neel

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Germ line gain-of-function mutations in several members of the RAS/ERK pathway, including PTPN11, KRAS, and RAF1, cause the autosomal dominant genetic disorder Noonan Syndrome (NS). NS patients are at increased risk of leukemia/myeloproliferative disease and possibly some solid tumors, such as neuroblastoma. Recently, SOS1 gain of function mutations have also been shown to cause NS. Somatic PTPN11, KRAS, and RAF1 mutations occur (although at different frequencies) in a variety of sporadic neoplasms, but whether SOS1 mutations are associated with human cancer has not been evaluated. We sequenced DNA from a total of 810 primary malignancies, including pancreatic, lung, breast, and colon carcinomas, and acute myelogenous leukemia, as well as several neuroblastoma cell lines. From this large, diverse series, missense SOS1 mutations were identified in a single pancreatic tumor, one lung adenocarcinoma, and a T-cell acute lymphoblastic leukemia cell line. Our findings suggest that SOS1 is not a significant human oncogene in most cancers. Furthermore, NS patients with SOS1 mutations may not be at increased risk of developing cancer.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalGenes Chromosomes and Cancer
Issue number3
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Genetics
  • Cancer Research


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