Single nucleotide polymorphisms act as modifiers and correlate with the development of medullary and simultaneous medullary/papillary thyroid carcinomas in 2 large, non-related families with the RET V804M proto-oncogene mutation.
BACKGROUND
Single nucleotide polymorphisms (SNPs) may function as modifiers of the RET proto-oncogene, resulting in the expression of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). We present 2 non-related Italian-American families (Family 1, n = 107; Family 2, n = 31) with the RET V804M mutation. We have correlated the presence of specific SNPs and the rare RET V804M mutation to MTC, C-cell hyperplasia (CCH), and PTC.


METHODS
Sequencing was performed on exons 10, 11, and 13-16 of the RET proto-oncogene. The presence of MTC, CCH, and PTC were correlated to specific SNPs.


RESULTS
In both families, 3 SNPs in exon 11 (G691S), exon 13 (L769L), and exon 15 (S904S) were detected in 100% of patients with overt MTC. The SNP L769L was present in all patients including patients with PTC, MTC, and CCH.


CONCLUSIONS
SNP analysis revealed a similar pattern between the 2 families. SNPs in exon 11 (G691S) and exon 15 (S904S) appear to influence the development of MTC. A SNP in exon 13 (L769L) may serve as a modifier in the development of simultaneous MTC and PTC, as well as presentation of MTC, in patients with the RET V804M mutation.
Department of Surgery, Jersey Shore University Medical Center, Neptune, NJ 07754, USA. ashifrin@meridianhealth.com
Alexander L
AL
Shifrin
Jennifer B
JB
Ogilvie
Michael T
MT
Stang
Angela Musial
AM
Fay
Yen-Hong
YH
Kuo
Theodore
T
Matulewicz
Cristina Z
CZ
Xenachis
Jerome J
JJ
Vernick
D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma; D018278:Carcinoma, Neuroendocrine; D002291:Carcinoma, Papillary; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human