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Submitted on September 14, 2006
Accepted on March 29, 2007
Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, U.S.A.; The Affilated Hospital of Qingdao Medical College, Qingdao University, Qingdao, P. R. China, 266003; Changzheng Hospital, The Second Military Medical University, Shanghai, P. R. China; The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061 P. R. China
* To whom correspondence should be addressed. E-mail: mxing1{at}jhmi.edu.
Context: Genetic alterations in the PI3K/Akt pathway and their role in thyroid tumor pathogenesis in Chinese people remain undefined.
Objective: To examine the major genetic alterations and their relationship in the PI3K/Akt pathway in differentiated thyroid tumors in a Chinese cohort.
Design: We used real-time quantitative PCR for the analysis of PIK3CA copy gain and direct DNA sequencing for the detection of PIK3CA, RAS, and PTEN mutations on genomic DNA isolated from 234 thyroid tumors, including 31 follicular thyroid cancer (FTC), 141 papillary thyroid cancer (PTC), and 62 follicular thyroid adenoma (FTA).
Results: We found PIK3CA copy gain (defined as 4 or more copies) in 9/31(29%) FTC, 20/141 (14%) PTC, and 5/62 (8%) FTA; PIK3CA gene mutations in 4/31 (13%) FTC, 1/141 (1%) PTC, and 0/62 (0%) FTA; Ras mutations in 3/31 (10%) FTC and none of the 141 PTC and 62 FTA; and PTEN mutations in 2/31 (6%) FTC and 0/62 (0%) FTA. Collectively, 9/31(29%) FTC vs. 0/62(0%) FTA (p < 0.01) harbored one of the mutations and, when PIK3CA copy gain was included, 16/31 (52%) FTC vs. 5/62 (8%) FTA (p < 0.01) harbored any genetic alteration in the PI3K/Akt pathway. Mutual exclusivity was seen among all these PI3K/Akt-pathway-related genetic alterations in all thyroid tumors except for two cases that harbored two genetic alterations.
Conclusion: These data from a Chinese cohort provide further genetic evidence suggesting that dysregulated PI3K/Akt pathway plays a significant role in the pathogenesis of thyroid tumors, particularly FTC.
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