Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: a novel approach using real-time PCR with melting curve analysis in histopathologic material.
The possible causes and genetic mechanisms of pulmonary carcinoid tumor development are unclear. In this study, we examined genetic alterations at the MEN1 locus in archival material from 15 pulmonary carcinoids. We employed, for the first time in this setting, real-time PCR with melting curve analysis in order to identify loss of heterozygosity (LOH) or microsatellite instability (MI) in two polymorphic markers (PYGM, D11S449) at the MEN1 locus and one additional marker (D11S906) of a putative oncosuppressive region distal to the MEN1 gene. Sequencing data were available in a selected subset of tumors in order to verify the reliability of real-time PCR analysis. We observed LOH at PYGM in 38% of the cases and MI in 13.3% of the cases. Our data indicate that real-time PCR with melting curve analysis is a reliable technique for LOH and MI detection and indicate that genetic errors at the MEN1 locus but also distal to it may be involved in the development of sporadic pulmonary carcinoid tumors.
Vageli
Dimitra
D
Department of Pathology, Medical School, University of Thessaly, 41222 Larissa, Greece. vagelidim@med.uth.gr
Daniil
Zoe
Z
Dahabreh
Jubrail
J
Karagianni
Eleni
E
Liloglou
Triantafillos
T
Koukoulis
George
G
Gourgoulianis
Konstantinos
K
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002276:Carcinoid Tumor / Q000235:genetics / Q000473:pathology*; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013997:Time Factors; D044366:Transition Temperature
D004273:DNA, Neoplasm; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins