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Novel candidate tumour suppressor gene loci on chromosomes 11q23–24 and 22q13 involved in human insulinoma tumourigenesis
Author(s) -
Jonkers YMH,
Claessen SMH,
Feuth T,
Geurts van Kessel A,
Ramaekers FCS,
Veltman JA,
Speel EJM
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2072
Subject(s) - comparative genomic hybridization , insulinoma , biology , men1 , chromosome , cancer research , genetics , chromosome instability , gene , multiple endocrine neoplasia , pancreas , biochemistry
Abstract Insulinomas represent the predominant syndromic subtype of endocrine pancreatic tumours. Previous molecular studies have shown that gain of chromosome 9q rather than MEN1 gene mutation is an important early event in tumour development and that chromosomal instability is associated with metastatic disease. In order to identify new gene loci and to define further the critical genetic events in insulinoma tumourigenesis, 27 insulinomas were investigated by array‐based comparative genomic hybridization (array CGH) on 3.7 k genomic BAC arrays (resolution ≤1 Mb). Fluorescence in situ hybridization was used to validate alterations in a subset of tumours. Array CGH most frequently detected loss of chromosomes 11q and 22q and gains of chromosome 9q. The chromosomal regions of interest (CRI) included 11q24.1 (56%), 22q13.1 (67%), 22q13.31 (56%), and 9q32 (63%). Evaluation of the simultaneous occurrence of these aberrations in the individual tumours revealed that gain of 9q32 and loss of 22q13.1 are early genetic events in insulinomas, occurring independently of the other alterations. In tumours with increased genomic complexity, these alterations were often detected simultaneously, occurring in the same tumour cells. Losses of 11q24.1 and 22q13.31 were also associated with these more advanced tumour cases. The CRIs identified most likely harbour crucial candidate genes important in insulinoma tumourigenesis. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.