TY - JOUR
T1 - Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome
AU - Swarts, Dorian R A
AU - Claessen, Sandra M H
AU - Jonkers, Yvonne M H
AU - van Suylen, Robert-Jan
AU - Dingemans, Anne-Marie C
AU - de Herder, Wouter W.
AU - de Krijger, Ronald R.
AU - Smit, Egbert F
AU - Thunnissen, Frederik B. J. M.
AU - Seldenrijk, Cornelis A
AU - Vink, Aryan
AU - Perren, Aurel
AU - Ramaekers, Frans C S
AU - Speel, Ernst-Jan M
N1 - Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PY - 2011/9
Y1 - 2011/9
N2 - 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).
AB - 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).
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoid Tumor
KW - Chromosomes, Human, Pair 11
KW - Diploidy
KW - Female
KW - Gene Deletion
KW - Humans
KW - Lung Neoplasms
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Proto-Oncogene Proteins
KW - Young Adult
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.ajpath.2011.05.028
DO - 10.1016/j.ajpath.2011.05.028
M3 - Article
C2 - 21763262
SN - 0002-9440
VL - 179
SP - 1129
EP - 1137
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -