PMID- 10022819
OWN - NLM
STAT- MEDLINE
DCOM- 19990303
LR  - 20190607
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 6
DP  - 1999 Feb 11
TI  - Over-representation of a germline RET sequence variant in patients with sporadic 
      medullary thyroid carcinoma and somatic RET codon 918 mutation.
PG  - 1369-73
AB  - The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% 
      harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether 
      other RET sequence variants may be associated with or predispose to the 
      development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from 
      the germline and corresponding tumour from 50 patients to identify RET sequence 
      variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame 
      deletion in exon 15. More interestingly, we found that the rare polymorphism at 
      codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than 
      that in control individuals without sporadic medullary thyroid carcinoma 
      (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with 
      germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which 
      was more frequent than in patients with the more common c.2439C/C (89% vs 40%, 
      respectively; Fisher's exact test, P = 0.01). These findings suggest that the 
      rare sequence variant at codon 836 may somehow play a role in the genesis of 
      sporadic medullary thyroid carcinoma.
FAU - Gimm, O
AU  - Gimm O
AD  - Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State 
      University, Columbus 43210, USA.
FAU - Neuberg, D S
AU  - Neuberg DS
FAU - Marsh, D J
AU  - Marsh DJ
FAU - Dahia, P L
AU  - Dahia PL
FAU - Hoang-Vu, C
AU  - Hoang-Vu C
FAU - Raue, F
AU  - Raue F
FAU - Hinze, R
AU  - Hinze R
FAU - Dralle, H
AU  - Dralle H
FAU - Eng, C
AU  - Eng C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Codon)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Ret protein, Drosophila)
SB  - IM
MH  - Carcinoma, Medullary/etiology/*genetics
MH  - Codon
MH  - *Drosophila Proteins
MH  - Genetic Variation
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 2a/genetics
MH  - Point Mutation
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-ret
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Sequence Deletion
MH  - Thyroid Neoplasms/etiology/*genetics
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1038/sj.onc.1202418 [doi]
PST - ppublish
SO  - Oncogene. 1999 Feb 11;18(6):1369-73. doi: 10.1038/sj.onc.1202418.