title: Allelic alterations in pancreatic endocrine tumors identified by genome-wide single nucleotide polymorphism analysis.
abstract: Pancreatic endocrine tumors (PETs) are uncommon and the genetic alterations in these indolent tumors are not well characterized. Chromosomal imbalances are frequent in tumors but PETs have not been studied by high-density single nucleotide polymorphism (SNP) array. We used genome-wide high-density SNP array analysis to detect copy number alterations using matched tumor and non-neoplastic tissue samples from 15 patients with PETs. In our study, whole or partial loss of chromosomes 1, 3, 11, 22 was present in 40, 47, 53, 40% of tumors respectively, and gain of chromosomes 5, 7, 12, 14, 17, and 20 was present in 47, 60, 47, 53, 53, and 47% of tumors respectively. One tumor had loss of heterozygosity of chromosome 3 and another of chromosome 22 without copy number alterations, suggesting uniparental disomy due to non-disjunction and deletion or to chromosomal recombination. Chromosomal aberrations of the autosomal chromosomes were correlated with chromosomal loss or gain of other chromosomes (r>0.5, P<0.5). About 60% of PETs had high allelic imbalances (AI) defined by more than four chromosomal aberrations, and 40% of tumors had low AI. The PETs with high AI were larger: the mean tumor size with high AI was 5.4 +/- 3.1 cm compared with 2.3 +/- 1.3 cm for low AI (P = 0.03). Our study shows that genome-wide allelotyping is a powerful new tool for the analysis of AI in PETs.
authors.affiliation: Department of Pathology, MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Box 85, Houston, Texas 77030-4095, USA.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nagano
authors.forename: Do Ha
authors.initials: DH
authors.lastname: Kim
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jill A
authors.initials: JA
authors.lastname: White
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide