Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome

Dorian R A Swarts, Sandra M H Claessen, Yvonne M H Jonkers, Robert-Jan van Suylen, Anne-Marie C Dingemans, Wouter W. de Herder, Ronald R. de Krijger, Egbert F Smit, Frederik B. J. M. Thunnissen, Cornelis A Seldenrijk, Aryan Vink, Aurel Perren, Frans C S Ramaekers, Ernst-Jan M Speel

Research output: Contribution to journalArticleAcademicpeer-review

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).

Original languageEnglish
Pages (from-to)1129-1137
Number of pages9
JournalAmerican Journal of Pathology
Volume179
Issue number3
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoid Tumor
  • Chromosomes, Human, Pair 11
  • Diploidy
  • Female
  • Gene Deletion
  • Humans
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Swarts, Dorian R A ; Claessen, Sandra M H ; Jonkers, Yvonne M H ; van Suylen, Robert-Jan ; Dingemans, Anne-Marie C ; de Herder, Wouter W. ; de Krijger, Ronald R. ; Smit, Egbert F ; Thunnissen, Frederik B. J. M. ; Seldenrijk, Cornelis A ; Vink, Aryan ; Perren, Aurel ; Ramaekers, Frans C S ; Speel, Ernst-Jan M. / Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome. In: American Journal of Pathology. 2011 ; Vol. 179, No. 3. pp. 1129-1137.
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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).",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Carcinoid Tumor, Chromosomes, Human, Pair 11, Diploidy, Female, Gene Deletion, Humans, Lung Neoplasms, Male, Middle Aged, Prognosis, Proto-Oncogene Proteins, Young Adult, Journal Article, Research Support, Non-U.S. Gov't",
author = "Swarts, {Dorian R A} and Claessen, {Sandra M H} and Jonkers, {Yvonne M H} and {van Suylen}, Robert-Jan and Dingemans, {Anne-Marie C} and {de Herder}, {Wouter W.} and {de Krijger}, {Ronald R.} and Smit, {Egbert F} and Thunnissen, {Frederik B. J. M.} and Seldenrijk, {Cornelis A} and Aryan Vink and Aurel Perren and Ramaekers, {Frans C S} and Speel, {Ernst-Jan M}",
note = "Copyright {\circledC} 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2011",
month = "9",
doi = "10.1016/j.ajpath.2011.05.028",
language = "English",
volume = "179",
pages = "1129--1137",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Science",
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Swarts, DRA, Claessen, SMH, Jonkers, YMH, van Suylen, R-J, Dingemans, A-MC, de Herder, WW, de Krijger, RR, Smit, EF, Thunnissen, FBJM, Seldenrijk, CA, Vink, A, Perren, A, Ramaekers, FCS & Speel, E-JM 2011, 'Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome', American Journal of Pathology, vol. 179, no. 3, pp. 1129-1137. https://doi.org/10.1016/j.ajpath.2011.05.028

Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome. / Swarts, Dorian R A; Claessen, Sandra M H; Jonkers, Yvonne M H; van Suylen, Robert-Jan; Dingemans, Anne-Marie C; de Herder, Wouter W.; de Krijger, Ronald R.; Smit, Egbert F; Thunnissen, Frederik B. J. M.; Seldenrijk, Cornelis A; Vink, Aryan; Perren, Aurel; Ramaekers, Frans C S; Speel, Ernst-Jan M.

In: American Journal of Pathology, Vol. 179, No. 3, 09.2011, p. 1129-1137.

Research output: Contribution to journalArticleAcademicpeer-review

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

VL - 179

SP - 1129

EP - 1137

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -