PMID- 19847891
OWN - NLM
STAT- MEDLINE
DCOM- 20100224
LR  - 20161125
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 49
IP  - 2
DP  - 2010 Feb
TI  - Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline 
      mutation p.Asp820Tyr develop through different cytogenetic progression pathways.
PG  - 91-8
LID - 10.1002/gcc.20720 [doi]
AB  - Hereditary gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal 
      dominant genetic disorder originated by germline mutations in the KIT or PDGFRA 
      genes. We report the third family with hereditary predisposition to GIST due to 
      the KIT Exon 17 germline mutation p.Asp820Tyr and characterize the cytogenetic 
      progression pathways followed by different GIST sharing the same primary genetic 
      event, using a combination of chromosome banding, comparative genomic 
      hybridization (CGH), and fluorescence in situ hybridization (FISH) analyses. The 
      missense mutation p.Asp820Tyr was detected in the proband's rectal and gastric 
      GIST, as well as in his aunt's GIST epiplon metastasis. The mutation p.Asp820Tyr 
      was subsequently also found in the proband's peripheral blood DNA, as well as in 
      that of 4 of 10 relatives thus far analyzed. CGH analysis revealed loss of 14q 
      and 15q in the proband's gastric lesion, whereas FISH analysis of the proband's 
      rectal GIST did not detect loss of 14q and 15q, but instead loss of 4q and 22q 
      and gain of 20q, indicating that the two tumors were independent GIST. Chromosome 
      banding and CGH analyses of the aunt's GIST epiplon metastasis revealed multiple 
      cytogenetic alterations, including 1p loss, but none in common with the two 
      proband's GIST. We conclude that, although the patients share the same KIT Exon 
      17 germline mutation, the multiple GIST analyzed followed different pathogenetic 
      progression pathways, each of which did not significantly differ from what has 
      been described in sporadic GIST.
FAU - Veiga, Isabel
AU  - Veiga I
AD  - Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
FAU - Silva, Mara
AU  - Silva M
FAU - Vieira, Joana
AU  - Vieira J
FAU - Pinto, Carla
AU  - Pinto C
FAU - Pinheiro, Manuela
AU  - Pinheiro M
FAU - Torres, Lurdes
AU  - Torres L
FAU - Soares, Marta
AU  - Soares M
FAU - Santos, Lucio
AU  - Santos L
FAU - Duarte, Hugo
AU  - Duarte H
FAU - Bastos, Artur L
AU  - Bastos AL
FAU - Coutinho, Camila
AU  - Coutinho C
FAU - Dinis, Jose
AU  - Dinis J
FAU - Lopes, Carlos
AU  - Lopes C
FAU - Teixeira, Manuel R
AU  - Teixeira MR
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Amino Acid Substitution
MH  - Chromosomes, Human, Pair 14/genetics
MH  - Chromosomes, Human, Pair 15/genetics
MH  - Comparative Genomic Hybridization
MH  - Exons/*genetics
MH  - Family
MH  - Female
MH  - Gastrointestinal Stromal Tumors/diagnostic imaging/*genetics/pathology/surgery
MH  - Germ-Line Mutation
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Pedigree
MH  - Pigmentation Disorders/genetics
MH  - Positron-Emission Tomography
MH  - Proto-Oncogene Proteins c-kit/*genetics
MH  - Radiography
MH  - Receptor, Platelet-Derived Growth Factor alpha/*genetics
EDAT- 2009/10/23 06:00
MHDA- 2010/02/25 06:00
CRDT- 2009/10/23 06:00
PHST- 2009/10/23 06:00 [entrez]
PHST- 2009/10/23 06:00 [pubmed]
PHST- 2010/02/25 06:00 [medline]
AID - 10.1002/gcc.20720 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2010 Feb;49(2):91-8. doi: 10.1002/gcc.20720.