PMID- 10522989
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20190607
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 10
DP  - 1999 Oct
TI  - A novel case of multiple endocrine neoplasia type 2A associated with two de novo 
      mutations of the RET protooncogene.
PG  - 3522-7
AB  - We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A)
      associated with two mutations of the protooncogene RET. One affects codon 634 and
      causes a cysteine to arginine substitution; the second at codon 640 causes an
      alanine to glycine substitution in the transmembrane region. The two mutations
      were present on the same RET allele and were detected in germline and tumor DNA. 
      Both mutations were de novo, i.e. they were not found in the DNA of the parents
      or relatives. Immunohistochemical and RT-PCR analysis showed that the
      pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line
      established from the tumor and propagated in culture sustained the expression of 
      RET and calcitonin, as did the original pheochromocytoma. Because the patient
      presented with medullary thyroid carcinoma and pheochromocytoma without
      parathyroid gland involvement, we speculate that this clinical picture could be
      correlated with the two RET mutations and to the unusual calcitonin production.
      This is the first report of a MEN 2A case due to two mutations of the RET gene
      and associated with a calcitonin-producing pheochromocytoma.
FAU - Tessitore, A
AU  - Tessitore A
AD  - Dipartimento di Biochimica e Biotecnologie Mediche e Ceinge, Centro di Ingegneria
      Genetica, Universita degli Studi di Napoli Federico II, Italy.
FAU - Sinisi, A A
AU  - Sinisi AA
FAU - Pasquali, D
AU  - Pasquali D
FAU - Cardone, M
AU  - Cardone M
FAU - Vitale, D
AU  - Vitale D
FAU - Bellastella, A
AU  - Bellastella A
FAU - Colantuoni, V
AU  - Colantuoni V
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Drosophila Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 9007-12-9 (Calcitonin)
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  - Adrenal Gland Neoplasms/genetics/metabolism/pathology
MH  - Adult
MH  - Alleles
MH  - Amino Acid Sequence/genetics
MH  - Amino Acid Substitution
MH  - Base Sequence/genetics
MH  - Calcitonin/metabolism
MH  - DNA Mutational Analysis
MH  - *Drosophila Proteins
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Multiple Endocrine Neoplasia Type 2a/*genetics/metabolism/pathology
MH  - Mutation/*genetics
MH  - Pheochromocytoma/genetics/metabolism/pathology
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-ret
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Tumor Cells, Cultured
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1210/jcem.84.10.6056 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Oct;84(10):3522-7. doi: 10.1210/jcem.84.10.6056.