Mutational Spectrum of Multiple Endocrine Neoplasia Type 2 and Sporadic Medullary Thyroid Carcinoma in Taiwan

Chang, Chin-Feng; Yang, Wei-Shiung; Su, Yi-Ning; Wu, I-Ling; Chang, Tien-Chun

doi:10.1016/S0929-6646(09)60084-X

« Previous Next »Journal of the Formosan Medical Association
Volume 108, Issue 5 , Pages 402-408, May 2009

Mutational Spectrum of Multiple Endocrine Neoplasia Type 2 and Sporadic Medullary Thyroid Carcinoma in Taiwan

Chin-Feng Chang
- Department of Laboratory Medicine, National Taiwan University Hospital;, Taipei, Taiwan
- Department of Genetic Counseling Program, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Wei-Shiung Yang
- Department of Internal Medicine, National Taiwan University Hospital;, Taipei, Taiwan
- Department of Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
- Department of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Genetic Counseling Program, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Yi-Ning Su
- Department of Medical Genetics, National Taiwan University Hospital;, Taipei, Taiwan
- Department of Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
- Department of Genetic Counseling Program, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
I-Ling Wu
- Department of Internal Medicine, National Taiwan University Hospital;, Taipei, Taiwan
- Department of Genetic Counseling Program, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Tien-Chun Chang
- Department of Internal Medicine, National Taiwan University Hospital;, Taipei, Taiwan
- Department of Medicine, National Taiwan University, Taipei, Taiwan
- Correspondence to: Dr Tien-Chun Chang, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan

Received 16 May 2008; received in revised form 24 September 2008; accepted 9 December 2008.

Background/Purpose

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer predisposition syndrome, and > 95% of MEN 2 patients carry rearranged during transfection (RET) protooncogene mutants. We aimed to elucidate the genotype and phenotype relationship of RET proto-oncogene mutations in Taiwanese subjects with medullary thyroid cancer (MTC).

Methods

We genotyped the MEN-2-associated germ-line mutations by PCR-based sequencing of the RET gene. DNA was extracted from a total of 69 members from eight unrelated families with individuals affected by MTC, and from seven sporadic cases of MTC.

Results

RET mutations were found in four MEN 2A families, all at codon 634 (one with C > R, two with C > F, and one with C > W). One MEN 2A patient carried a de novo mutation at codon 634 (C > R). In two families of MEN 2B, all carried the mutation at codon 918 (M > T). These two cases of MEN 2B were all de novo mutations. One family of familial MTC or unclassified MEN 2 carried the codon 620 (C > F) mutation. Among the seven sporadic cases of MTC, none was found to carry any mutation in hotspot exons. Only two non-synonymous variants (T278N/exon 4 and D489N/exon 7) were found in two cases. However, these two variants were not uncommon in our elderly population.

Conclusion

We found that all eight MTC patients with a family history or with the other phenotypes of MEN 2 had RET mutations, whereas no significant RET mutation was found in seven patients with isolated MTC without family history and other endocrine diseases. Molecular scanning of the RET gene in MEN 2 and MTC in Taiwanese patients probably should be limited to exons 10, 11 and 16, initially to be cost-effective.

Key Words: human , multiple endocrine neoplasia type 2A , multiple endocrine neoplasia type 2B , mutation , RET protein , thyroid neoplasms