TY - JOUR
T1 - SOS1 mutations are rare in human malignancies
T2 - Implications for Noonan syndrome patients
AU - Swanson, Kenneth D.
AU - Winter, Jordan M.
AU - Reis, Marcelo
AU - Bentires-Alj, Mohamed
AU - Greulich, Heidi
AU - Grewal, Rupinder
AU - Hruban, Ralph H.
AU - Yeo, Charles J.
AU - Yassin, Yosuf
AU - Iartchouk, Oleg
AU - Montgomery, Kate
AU - Whitman, Susan P.
AU - Caligiuri, Michael A.
AU - Loh, Mignon L.
AU - Gilliland, D. Gary
AU - Look, A. Thomas
AU - Kucherlapati, Raju
AU - Kern, Scott E.
AU - Meyerson, Matthew
AU - Neel, Benjamin G.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
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U2 - 10.1002/gcc.20527
DO - 10.1002/gcc.20527
M3 - Article
C2 - 18064648
AN - SCOPUS:38549168319
SN - 1045-2257
VL - 47
SP - 253
EP - 259
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 3
ER -