Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients

Silje H. Nordgard, Fredrik E. Johansen, Grethe I. G. Alnæs, Elmar Bucher, Ann-Christine Syvänen, Bjørn Naume, Anne-Lise Børresen-Dale (Corresponding Author), Vessela N. Kristensen

Research output: Contribution to journalArticleScientificpeer-review

62 Citations (Scopus)

Abstract

Breast carcinomas are characterized by DNA copy number alterations (CNAs) with biological and clinical significance. This explorative study integrated CNA, expression, and germline genotype data of 112 early‐stage breast cancer patients. Recurrent CNAs differed substantially between tumor subtypes classified according to expression pattern. Deletion of 16q was overrepresented in Luminal A, and a predictor of good prognosis, both overall and for the nonluminal A subgroups. The deleted region most significantly associated with survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38, whose expression was strongly correlated with the deletion. The area most frequently deleted resided on 16q23.1, 3.5 MB downstream of the area most significantly associated with survival, and included the tumor suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4. Whole‐genome association analysis identified germline single nucleotide polymorphisms (SNPs) and their corresponding haplotypes, residing on several different chromosomes, to be associated with deletion of 16q. The genes where these SNPs reside encode proteins involved in the extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).
Original languageEnglish
Pages (from-to)680 - 696
Number of pages17
JournalGenes, Chromosomes and Cancer
Volume47
Issue number8
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Haplotypes
Genome
Breast Neoplasms
Messenger RNA
Single Nucleotide Polymorphism
Survival
Genes
Chromosomal Instability
Tumor Suppressor Genes
Extracellular Matrix
Cell Cycle
Chromosomes
Genotype
DNA
Neoplasms
Proteins

Keywords

  • carcinomas
  • breast cancer
  • CNAs
  • gene expression

Cite this

Nordgard, Silje H. ; Johansen, Fredrik E. ; Alnæs, Grethe I. G. ; Bucher, Elmar ; Syvänen, Ann-Christine ; Naume, Bjørn ; Børresen-Dale, Anne-Lise ; Kristensen, Vessela N. / Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients. In: Genes, Chromosomes and Cancer. 2008 ; Vol. 47, No. 8. pp. 680 - 696.
@article{d72e13e9acf84ec2b6867d640cc99795,
title = "Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients",
abstract = "Breast carcinomas are characterized by DNA copy number alterations (CNAs) with biological and clinical significance. This explorative study integrated CNA, expression, and germline genotype data of 112 early‐stage breast cancer patients. Recurrent CNAs differed substantially between tumor subtypes classified according to expression pattern. Deletion of 16q was overrepresented in Luminal A, and a predictor of good prognosis, both overall and for the nonluminal A subgroups. The deleted region most significantly associated with survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38, whose expression was strongly correlated with the deletion. The area most frequently deleted resided on 16q23.1, 3.5 MB downstream of the area most significantly associated with survival, and included the tumor suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4. Whole‐genome association analysis identified germline single nucleotide polymorphisms (SNPs) and their corresponding haplotypes, residing on several different chromosomes, to be associated with deletion of 16q. The genes where these SNPs reside encode proteins involved in the extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).",
keywords = "carcinomas, breast cancer, CNAs, gene expression",
author = "Nordgard, {Silje H.} and Johansen, {Fredrik E.} and Aln{\ae}s, {Grethe I. G.} and Elmar Bucher and Ann-Christine Syv{\"a}nen and Bj{\o}rn Naume and Anne-Lise B{\o}rresen-Dale and Kristensen, {Vessela N.}",
year = "2008",
doi = "10.1002/gcc.20569",
language = "English",
volume = "47",
pages = "680 -- 696",
journal = "Genes, Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "8",

}

Nordgard, SH, Johansen, FE, Alnæs, GIG, Bucher, E, Syvänen, A-C, Naume, B, Børresen-Dale, A-L & Kristensen, VN 2008, 'Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients', Genes, Chromosomes and Cancer, vol. 47, no. 8, pp. 680 - 696. https://doi.org/10.1002/gcc.20569

Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients. / Nordgard, Silje H.; Johansen, Fredrik E.; Alnæs, Grethe I. G.; Bucher, Elmar; Syvänen, Ann-Christine; Naume, Bjørn; Børresen-Dale, Anne-Lise (Corresponding Author); Kristensen, Vessela N.

In: Genes, Chromosomes and Cancer, Vol. 47, No. 8, 2008, p. 680 - 696.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients

AU - Nordgard, Silje H.

AU - Johansen, Fredrik E.

AU - Alnæs, Grethe I. G.

AU - Bucher, Elmar

AU - Syvänen, Ann-Christine

AU - Naume, Bjørn

AU - Børresen-Dale, Anne-Lise

AU - Kristensen, Vessela N.

PY - 2008

Y1 - 2008

N2 - Breast carcinomas are characterized by DNA copy number alterations (CNAs) with biological and clinical significance. This explorative study integrated CNA, expression, and germline genotype data of 112 early‐stage breast cancer patients. Recurrent CNAs differed substantially between tumor subtypes classified according to expression pattern. Deletion of 16q was overrepresented in Luminal A, and a predictor of good prognosis, both overall and for the nonluminal A subgroups. The deleted region most significantly associated with survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38, whose expression was strongly correlated with the deletion. The area most frequently deleted resided on 16q23.1, 3.5 MB downstream of the area most significantly associated with survival, and included the tumor suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4. Whole‐genome association analysis identified germline single nucleotide polymorphisms (SNPs) and their corresponding haplotypes, residing on several different chromosomes, to be associated with deletion of 16q. The genes where these SNPs reside encode proteins involved in the extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).

AB - Breast carcinomas are characterized by DNA copy number alterations (CNAs) with biological and clinical significance. This explorative study integrated CNA, expression, and germline genotype data of 112 early‐stage breast cancer patients. Recurrent CNAs differed substantially between tumor subtypes classified according to expression pattern. Deletion of 16q was overrepresented in Luminal A, and a predictor of good prognosis, both overall and for the nonluminal A subgroups. The deleted region most significantly associated with survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38, whose expression was strongly correlated with the deletion. The area most frequently deleted resided on 16q23.1, 3.5 MB downstream of the area most significantly associated with survival, and included the tumor suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4. Whole‐genome association analysis identified germline single nucleotide polymorphisms (SNPs) and their corresponding haplotypes, residing on several different chromosomes, to be associated with deletion of 16q. The genes where these SNPs reside encode proteins involved in the extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).

KW - carcinomas

KW - breast cancer

KW - CNAs

KW - gene expression

U2 - 10.1002/gcc.20569

DO - 10.1002/gcc.20569

M3 - Article

VL - 47

SP - 680

EP - 696

JO - Genes, Chromosomes and Cancer

JF - Genes, Chromosomes and Cancer

SN - 1045-2257

IS - 8

ER -