期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 98, 期 2, 页码 E364-E369出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2012-2703
关键词
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资金
- National Institutes of Health [RC2DE020957, CA57345, CA121113]
- American Cancer Society [RSGM-11-084-01-TBG]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [09/15386-6]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [401990/2010-9]
- American Association for Cancer Research Stand Up to Cancer-Dream Team Translational Cancer Research Grant
- Burroughs Wellcome Fund Career Award for Medical Scientists
- Johns Hopkins Clinician Scientist Award
- Virginia and D. K. Ludwig Fund for Cancer Research
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [09/15386-6] Funding Source: FAPESP
Context: Medullary thyroid cancer (MTC) is a rare thyroid cancer that can occur sporadically or as part of a hereditary syndrome. Objective: To explore the genetic origin of MTC, we sequenced the protein coding exons of approximately 21,000 genes in 17 sporadic MTCs. Patients and Design: We sequenced the exomes of 17 sporadic MTCs and validated the frequency of all recurrently mutated genes and other genes of interest in an independent cohort of 40 MTCs comprised of both sporadic and hereditary MTC. Results: We discovered 305 high-confidence mutations in the 17 sporadic MTCs in the discovery phase, or approximately 17.9 somatic mutations per tumor. Mutations in RET, HRAS, and KRAS genes were identified as the principal driver mutations in MTC. All of the other additional somatic mutations, including mutations in spliceosome and DNA repair pathways, were not recurrent in additional tumors. Tumors without RET, HRAS, or KRAS mutations appeared to have significantly fewer mutations overall in protein coding exons. Conclusions: Approximately 90% of MTCs had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in MTC. Relatively few mutations overall and no commonly recurrent driver mutations other than RET, HRAS, and KRAS were seen in the MTC exome. (J Clin Endocrinol Metab 98: E364-E369, 2013)
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