Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer

Publication: Research - peer-reviewJournal article – Annual report year: 2011

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Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer. / Birkbak, Nicolai Juul; Eklund, Aron Charles; Li, Qiyuan; McClelland, Sarah E.; Endesfelder, David; Tan, Patrick; Tan, Iain B.; Richardson, Andrea L.; Szallasi, Zoltan Imre; Swanton, Charles.

In: Cancer Research, Vol. 71, No. 10, 2011, p. 3447-3452.

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Harvard

Birkbak, NJ, Eklund, AC, Li, Q, McClelland, SE, Endesfelder, D, Tan, P, Tan, IB, Richardson, AL, Szallasi, ZI & Swanton, C 2011, 'Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer' Cancer Research, vol 71, no. 10, pp. 3447-3452., 10.1158/0008-5472.CAN-10-3667

APA

CBE

Birkbak NJ, Eklund AC, Li Q, McClelland SE, Endesfelder D, Tan P, Tan IB, Richardson AL, Szallasi ZI, Swanton C. 2011. Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer. Cancer Research. 71(10):3447-3452. Available from: 10.1158/0008-5472.CAN-10-3667

MLA

Vancouver

Author

Birkbak, Nicolai Juul; Eklund, Aron Charles; Li, Qiyuan; McClelland, Sarah E.; Endesfelder, David; Tan, Patrick; Tan, Iain B.; Richardson, Andrea L.; Szallasi, Zoltan Imre; Swanton, Charles / Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer.

In: Cancer Research, Vol. 71, No. 10, 2011, p. 3447-3452.

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Bibtex

@article{79ace256d7044ac0a3e6a02c08010fcc,
title = "Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer",
publisher = "American Association for Cancer Research (A A C R)",
author = "Birkbak, {Nicolai Juul} and Eklund, {Aron Charles} and Qiyuan Li and McClelland, {Sarah E.} and David Endesfelder and Patrick Tan and Tan, {Iain B.} and Richardson, {Andrea L.} and Szallasi, {Zoltan Imre} and Charles Swanton",
note = "Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).",
year = "2011",
doi = "10.1158/0008-5472.CAN-10-3667",
volume = "71",
number = "10",
pages = "3447--3452",
journal = "Cancer Research",
issn = "0008-5472",

}

RIS

TY - JOUR

T1 - Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer

A1 - Birkbak,Nicolai Juul

A1 - Eklund,Aron Charles

A1 - Li,Qiyuan

A1 - McClelland,Sarah E.

A1 - Endesfelder,David

A1 - Tan,Patrick

A1 - Tan,Iain B.

A1 - Richardson,Andrea L.

A1 - Szallasi,Zoltan Imre

A1 - Swanton,Charles

AU - Birkbak,Nicolai Juul

AU - Eklund,Aron Charles

AU - Li,Qiyuan

AU - McClelland,Sarah E.

AU - Endesfelder,David

AU - Tan,Patrick

AU - Tan,Iain B.

AU - Richardson,Andrea L.

AU - Szallasi,Zoltan Imre

AU - Swanton,Charles

PB - American Association for Cancer Research (A A C R)

PY - 2011

Y1 - 2011

N2 - Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models elevated CIN negatively impacts upon organism fitness, and is poorly tolerated by cancer cells. To better understand this seemingly contradictory relationship between CIN and cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts. Tumors with extreme CIN, defined as the highest quartile CIN70 score, were predominantly of the estrogen receptor negative (ER-), basal-like phenotype and displayed the highest chromosomal structural complexity and chromosomal numerical instability. We found that the extreme CIN/ER- tumors were associated with improved prognosis relative to tumors with intermediate CIN70 scores in the third quartile. We also observed this paradoxical relationship between CIN and prognosis in ovarian, gastric, and non-small cell lung cancer, with poorest outcome in tumors with intermediate, rather than extreme, CIN70 scores. These results suggest a nonmonotonic relationship between gene signature expression and HR for survival outcome, which may explain the difficulties encountered in the identification of prognostic expression signatures in ER- breast cancer. Furthermore, the data are consistent with the intolerance of excessive CIN in carcinomas and provide a plausible strategy to define distinct prognostic patient cohorts with ER- breast cancer. Inclusion of a surrogate measurement of CIN may improve cancer risk stratification and future therapeutic approaches. Cancer Res; 71(10); 3447-52. (C) 2011 AACR.

AB - Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models elevated CIN negatively impacts upon organism fitness, and is poorly tolerated by cancer cells. To better understand this seemingly contradictory relationship between CIN and cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts. Tumors with extreme CIN, defined as the highest quartile CIN70 score, were predominantly of the estrogen receptor negative (ER-), basal-like phenotype and displayed the highest chromosomal structural complexity and chromosomal numerical instability. We found that the extreme CIN/ER- tumors were associated with improved prognosis relative to tumors with intermediate CIN70 scores in the third quartile. We also observed this paradoxical relationship between CIN and prognosis in ovarian, gastric, and non-small cell lung cancer, with poorest outcome in tumors with intermediate, rather than extreme, CIN70 scores. These results suggest a nonmonotonic relationship between gene signature expression and HR for survival outcome, which may explain the difficulties encountered in the identification of prognostic expression signatures in ER- breast cancer. Furthermore, the data are consistent with the intolerance of excessive CIN in carcinomas and provide a plausible strategy to define distinct prognostic patient cohorts with ER- breast cancer. Inclusion of a surrogate measurement of CIN may improve cancer risk stratification and future therapeutic approaches. Cancer Res; 71(10); 3447-52. (C) 2011 AACR.

UR - http://cancerres.aacrjournals.org/

U2 - 10.1158/0008-5472.CAN-10-3667

DO - 10.1158/0008-5472.CAN-10-3667

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 10

VL - 71

SP - 3447

EP - 3452

ER -