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Novel c‐KIT germline mutation in a family with gastrointestinal stromal tumors and cutaneous hyperpigmentation
Author(s) -
Carballo Miguel,
Roig Ignasi,
Aguilar Francesc,
Pol Maria Antonia,
Gamundi María José,
Hernan Imma,
MartinezGimeno María
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30388
Subject(s) - gist , germline mutation , mutation , exon , biology , cancer research , gene mutation , germline , gene duplication , pathology , genetics , gene , medicine , stromal cell
Mutations in the c‐KIT gene have been identified in many sporadic and familial cases of gastrointestinal stromal tumor (GIST). We report a familial case of GIST with cutaneous hyperpigmentation associated with a novel germline mutation in the c‐KIT gene. Screening for mutations in exon 11 of the c‐KIT gene in genomic DNA from tumors and peripheral blood of the members of a family with GISTs was undertaken by direct genomic sequencing. Tumors from GIST patients were analyzed histologically and immunohistochemically. Clinical examination of GIST patients was also performed to detect other systemic diseases associated with c‐KIT mutations. Histological study showed that the tumors were GISTs expressing CD34 and c‐KIT protein. This GIST‐hyperpigmentation disease was associated in the family with a germline mutation in the c‐KIT gene. The mutation is a duplication of the sequence CAACTT located in exon 11 of the c‐KIT gene, which introduces two extra glutamine and leucine residues in the encoding protein between positions 576 and 577. This Spanish family was affected with GISTs and cutaneous hyperpigmentation associated with a novel germline mutation Leu576_Pro577insGlnLeu in the juxtamembrane domain of the c‐KIT receptor. These types of mutation in the c‐KIT gene activate the tyrosine kinase activity of the c‐KIT receptor and induce constitutive signaling leading to GISTs, in some cases associated with cutaneous hyperpigmentation. © 2004 Wiley‐Liss, Inc.