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Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course.

Abstract：

:The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which suggests the involvement of additional modulators of the disease. However, genetic factors responsible for this heterogeneity of the MTC clinical course still remain unknown. The aim of this study was to determine if polymorphic variants or specific haplotypes of the RET gene may modify the MTC clinical course. We genotyped the following loci: c.73+9277T>C, c.135G>A, c.1296A>G, c.2071G>A, c.2307T>C, c.2508C>T and c.2712C>G in 142 MTC patients and controls. We demonstrated considerable differences in the genotypes distribution within c.73+9277T>C, c.135G>A and c.2307T>C loci Our results show that the c.73+9277T variant associated with a decreased activity of the MCS+9.7 RET enhancer is rare in hereditary MTC patients with primary hyperparathyroidism, and thus, may influence the MTC clinical picture. The decreased activity of the RET promoter enhancer reduces RET expression level and may counterbalance the activating mutation in this gene. Frequent co-occurrence of the c.73+9277T allele with p.E768D, p.Y791F, p.V804M or p.R844Q RET mutations may be associated with their attenuation and milder clinical picture of the disease. Haplotypes analysis showed that C-G-A-G-T-(C)-C (c.73+9277T>C - c.135G>A - c.1296A>G - c.2071G>A - c.2307T>G - (c.2508C>T) - c.2712C>G) alleles combination predisposes to pheochromocytomas and primary hyperparathyroidism. We consider that RET haplotypes defining may become an auxiliary diagnostic tool in MTC patients.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Kaczmarek-Ryś M,Ziemnicka K,Pławski A,Budny B,Michalak M,Hryhorowicz S,Hoppe-Gołębiewska J,Boruń P,Gołąb M,Czetwertyńska M,Sromek M,Szalata M,Ruchała M,Słomski R

doi

10.1530/ERC-17-0452

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

421-436

issue

eissn

1351-0088

issn

1479-6821

pii

ERC-17-0452

journal_volume

pub_type

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Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course.