Influence of whole arm loss of chromosome 16q on gene expression patterns in oestrogen receptor-positive, invasive breast cancer.
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Influence of whole arm loss of chromosome 16q on gene expression patterns in oestrogen receptor-positive, invasive breast cancer. / Hungermann, Daniela; Schmidt, Hartmut; Natrajan, Rachel; Tidow, Nicola; Poos, Kathrin; Reis-Filho, Jorge S; Brandt, Burkhard; Buerger, Horst; Korsching, Eberhard.
in: J PATHOL, Jahrgang 224, Nr. 4, 4, 2011, S. 517-528.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Influence of whole arm loss of chromosome 16q on gene expression patterns in oestrogen receptor-positive, invasive breast cancer.
AU - Hungermann, Daniela
AU - Schmidt, Hartmut
AU - Natrajan, Rachel
AU - Tidow, Nicola
AU - Poos, Kathrin
AU - Reis-Filho, Jorge S
AU - Brandt, Burkhard
AU - Buerger, Horst
AU - Korsching, Eberhard
PY - 2011
Y1 - 2011
N2 - A whole chromosome arm loss of 16q belongs to the most frequent and earliest chromosomal alterations in invasive and in situ breast cancers of all common subtypes. Besides E-cadherin, several putative tumour suppressor genes residing on 16q in breast cancer have been investigated. However, the significance of these findings has remained unclear. Thus, other mechanisms leading to gene loss of function (eg haploinsufficiency, or distortion of multiple regulative subnetworks) remain to be tested as a hypothesis. To define the effect on gene expression of whole-arm loss of chromosome 16q in invasive breast cancer, we performed global gene expression analysis on a series of 18 genetically extensively characterized invasive ductal breast carcinomas and verified the results by quantitative real-time PCR (qRT-PCR). The distribution of the differential genes across the genome and their expression status was studied. A second approach by qRT-PCR in an independent series of 30 breast carcinomas helped to narrow down the observed effect. Whole-arm chromosome 16q losses, irrespective of other chromosomal changes, are associated with decreased expression of a number of candidate genes located on 16q (eg CDA08, CGI-128, SNTB2, NQO1, SF3B3, KIAA0174, ATBF1, GABARAPL2, KARS, GCSH, MBTPS1 and ZDHHC7) in breast carcinomas with a low degree of genetic instability. qRT-PCR provided evidence to suggest that the expression of these genes was reduced in a gene dosage-dependent manner. The differential expression of the candidate genes according to the chromosomal 16q-status vanished in genetically advanced breast cancer cases and changed ER status. These results corroborate previous reports about the importance of whole-arm loss of chromosome 16q in breast carcinogenesis and give evidence for the first time that haploinsufficiency, in the sense of a gene dosage effect, might be an important contributing factor in the early steps of breast carcinogenesis.
AB - A whole chromosome arm loss of 16q belongs to the most frequent and earliest chromosomal alterations in invasive and in situ breast cancers of all common subtypes. Besides E-cadherin, several putative tumour suppressor genes residing on 16q in breast cancer have been investigated. However, the significance of these findings has remained unclear. Thus, other mechanisms leading to gene loss of function (eg haploinsufficiency, or distortion of multiple regulative subnetworks) remain to be tested as a hypothesis. To define the effect on gene expression of whole-arm loss of chromosome 16q in invasive breast cancer, we performed global gene expression analysis on a series of 18 genetically extensively characterized invasive ductal breast carcinomas and verified the results by quantitative real-time PCR (qRT-PCR). The distribution of the differential genes across the genome and their expression status was studied. A second approach by qRT-PCR in an independent series of 30 breast carcinomas helped to narrow down the observed effect. Whole-arm chromosome 16q losses, irrespective of other chromosomal changes, are associated with decreased expression of a number of candidate genes located on 16q (eg CDA08, CGI-128, SNTB2, NQO1, SF3B3, KIAA0174, ATBF1, GABARAPL2, KARS, GCSH, MBTPS1 and ZDHHC7) in breast carcinomas with a low degree of genetic instability. qRT-PCR provided evidence to suggest that the expression of these genes was reduced in a gene dosage-dependent manner. The differential expression of the candidate genes according to the chromosomal 16q-status vanished in genetically advanced breast cancer cases and changed ER status. These results corroborate previous reports about the importance of whole-arm loss of chromosome 16q in breast carcinogenesis and give evidence for the first time that haploinsufficiency, in the sense of a gene dosage effect, might be an important contributing factor in the early steps of breast carcinogenesis.
KW - Humans
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Gene Dosage
KW - Neoplasm Invasiveness
KW - Breast Neoplasms/genetics/metabolism/pathology
KW - Carcinoma, Ductal, Breast/genetics/metabolism/pathology
KW - Chromosome Deletion
KW - Chromosomes, Human, Pair 16/genetics
KW - Comparative Genomic Hybridization/methods
KW - Gene Expression Profiling/methods
KW - Neoplasm Proteins/metabolism
KW - Oligonucleotide Array Sequence Analysis/methods
KW - Receptors, Estrogen/metabolism
KW - Reverse Transcriptase Polymerase Chain Reaction/methods
KW - Humans
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Gene Dosage
KW - Neoplasm Invasiveness
KW - Breast Neoplasms/genetics/metabolism/pathology
KW - Carcinoma, Ductal, Breast/genetics/metabolism/pathology
KW - Chromosome Deletion
KW - Chromosomes, Human, Pair 16/genetics
KW - Comparative Genomic Hybridization/methods
KW - Gene Expression Profiling/methods
KW - Neoplasm Proteins/metabolism
KW - Oligonucleotide Array Sequence Analysis/methods
KW - Receptors, Estrogen/metabolism
KW - Reverse Transcriptase Polymerase Chain Reaction/methods
M3 - SCORING: Journal article
VL - 224
SP - 517
EP - 528
JO - J PATHOL
JF - J PATHOL
SN - 0022-3417
IS - 4
M1 - 4
ER -