This Article Full Text Full Text (PDF) All Versions of this Article: 92/6/2387    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Xing, M. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Xing, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Thyroid Cancer Related Collections Endocrine Oncology Thyroid

High Prevalence and Mutual Exclusivity of Genetic Alterations in the Phosphatidylinositol-3-Kinase/Akt Pathway in Thyroid Tumors

Division of Endocrinology and Metabolism (Y.W., P.H., M.J., D.L., S.C., M.X.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; The Affiliated Hospital of Qingdao Medical College (Y.W., W.W., S.Z., S.Y., X.S., G.Z.), Qingdao University, Qingdao 266003, People’s Republic of China; Changzheng Hospital (H.Y.), The Second Military Medical University, Shanghai 200433, People’s Republic of China; and The First Affiliated Hospital of Medical College (B.S.), Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China

Address all correspondence and requests for reprints to: Michael Mingzhao Xing, M.D., Ph.D., Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: mxing1{at}jhmi.edu.

Context: Genetic alterations in the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and their role in thyroid tumor pathogenesis in Chinese people remain undefined.

Objective: The objective of the study was 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 four or more copies) in nine of 31 FTC (29%), 20 of 141 PTC (14%), and five of 62 FTA (8%); PIK3CA gene mutations in four of 31 FTC (13%), one of 141 PTC (1%), and none of 62 FTA (0%); Ras mutations in three of 31 FTC (10%) and none of the 141 PTC and 62 FTA; and PTEN mutations in two of 31 FTC (6%) and none of 62 FTA (0%). Collectively, nine of 31 FTC (29%) vs. none of 62 FTA (0%) (P < 0.01) harbored one of the mutations, and when PIK3CA copy gain was included, 16 of 31 FTC (52%) vs. five of 62 FTA (8%) (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.

This article has been cited by other articles:

				J. Abubaker, Z. Jehan, P. Bavi, M. Sultana, S. Al-Harbi, M. Ibrahim, A. Al-Nuaim, M. Ahmed, T. Amin, M. Al-Fehaily, et al. Clinicopathological Analysis of Papillary Thyroid Cancer with PIK3CA Alterations in a Middle Eastern Population J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 611 - 618. [Abstract] [Full Text] [PDF]

				N. Yeager, C. Brewer, K. Q. Cai, X.-X. Xu, and A. Di Cristofano Mammalian Target of Rapamycin Is the Key Effector of Phosphatidylinositol-3-OH Initiated Proliferative Signals in the Thyroid Follicular Epithelium Cancer Res., January 15, 2008; 68(2): 444 - 449. [Abstract] [Full Text] [PDF]

				L. Santarpia, A. K. El-Naggar, G. J. Cote, J. N. Myers, and S. I. Sherman Phosphatidylinositol 3-Kinase/Akt and Ras/Raf-Mitogen-Activated Protein Kinase Pathway Mutations in Anaplastic Thyroid Cancer J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 278 - 284. [Abstract] [Full Text] [PDF]

				D. W. Ball, N. Jin, D. M. Rosen, A. Dackiw, D. Sidransky, M. Xing, and B. D. Nelkin Selective Growth Inhibition in BRAF Mutant Thyroid Cancer by the Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4712 - 4718. [Abstract] [Full Text] [PDF]