title: Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome.
abstract: Carcinoids are slow-growing neuroendocrine tumors that, in the lung, can be subclassified as typical (TC) or atypical (AC). To identify genetic alterations that improve the prediction of prognosis, we investigated 34 carcinoid tumors of the lung (18 TCs, 15 ACs, and 1 unclassified) by using array comparative genomic hybridization (array CGH) on 3700 genomic bacterial artificial chromosome arrays (resolution ≤1 Mb). When comparing ACs with TCs, the data revealed: i) a significant difference in the average number of chromosome arms altered (9.6 versus 4.2, respectively; P = 0.036), with one subgroup of five ACs having more than 15 chromosome arms altered; ii) chromosomal changes in 30% of ACs or more with additions at 9q (≥1 Mb) and losses at 1p, 2q, 10q, and 11q; and iii) 11q deletions in 8 of 15 ACs versus 1 of 18 TCs (P = 0.004), which was confirmed via fluorescence in situ hybridization. The four critical regions of interest in 45% ACs or more comprised 11q14.1, 11q22.1-q22.3, 11q22.3-q23.2, and 11q24.2-q25, all telomeric of MEN1 at 11q13. Results were correlated with patient clinical data and long-term follow-up. Thus, there is a strong association of 11q22.3-q25 loss with poorer prognosis, alone or in combination with absence of 9q34.11 alterations (P = 0.0022 and P = 0.00026, respectively).
authors.affiliation: Department of Molecular Cell Biology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands. d.swarts@maastrichtuniversity.nl
authors.forename: Dorian R A
authors.initials: DR
authors.lastname: Swarts
authors.forename: Sandra M H
authors.initials: SM
authors.lastname: Claessen
authors.forename: Yvonne M H
authors.initials: YM
authors.lastname: Jonkers
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: van Suylen
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Frederik B J M
authors.initials: FB
authors.lastname: Thunnissen
authors.forename: Cornelis A
authors.initials: CA
authors.lastname: Seldenrijk
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Frans C S
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: Ernst-Jan M
authors.initials: EJ
authors.lastname: Speel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002276:Carcinoid Tumor / Q000235:genetics* / Q000401:mortality; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004171:Diploidy; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins