Different mechanisms of chromosome 16 loss of heterozygosity in well‐ versus poorly differentiated ductal breast cancer

Cleton‐Jansen, Anne‐Marie; Buerger, Horst; Haar, Natalja T. ter; Philippo, Katja; Vijver, Marc J. van de; Boecker, Werner; Smit, Vincent T.H.B.M.; Cornelisse, Cees J.

doi:10.1002/gcc.20070

Cited by 53 publications

(57 citation statements)

References 30 publications

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“…Combined global analysis of LOH and genomic copy number data showed that LOH in PCa correlates positively to copy loss. Our data showed no signs of uniparental disomy in LOH regions, as otherwise recently reported to be a common mechanism in advanced breast cancer (Murthy et al, 2002;Cleton-Jansen et al, 2004), acute myeloid leukaemia , medullablastoma (Langdon et al, 2006) and basal cell carcinomas (Teh et al, 2005). Loss of heterozygosity and concomitant copy loss at chromosomes 8p, 10q, 13q,16q and 21q were found with an equal frequency in both localised and metastatic tumours, and were not associated with tumour stage or grade.…”

Section: Discussionsupporting

confidence: 77%

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Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

et al. 2007

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Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in male subjects in Western countries. The widespread use of prostate-specific antigen (PSA) has increased the detection of this cancer form in earlier stages. Moreover, it has increased the need for new diagnostic procedures to be developed for patient stratification based on risk of progression. We analysed laser-microdissected prostate tumour tissue from 43 patients with histologically verified PCa, using the new high-resolution Affymetrix Mapping 50K single-nucleotide polymorphism array. The results showed six major loss of heterozygosity regions at chromosomes 6q14 -16, 8p23 -11, 10q23, 13q13 -21 and 16q21 -24 and a novel region at chromosome 21q22.2, all of which reveal concomitant copy number loss. Tumour development was further characterised by numerous novel genomic regions almost exclusively showing copy number loss. However, tumour progression towards a metastatic stage, as well as poor differentiation, was identified by specific patterns of copy number gains of genomic regions located at chromosomes 8q, 1q, 3q and 7q. Androgen ablation therapy was further characterised by copy gain at chromosomes 2p and 10q. In conclusion, patterns of allelic imbalance were discovered in PCa, consisting allelic loss as an early event in tumour development, and distinct patterns of allelic amplification related to tumour progression and poor differentiation.

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Section: Discussionsupporting

confidence: 77%

“…Recently it has been shown that LOH regions in the cancer genome often show two copies, despite the loss of one allele (Cleton-Jansen et al, 2004). We therefore tested the correlation between LOH and signal intensities for all samples showing LOH.…”

Section: Comparison Of Loh and Copy Number Alterations In Tumour Dnamentioning

confidence: 99%

Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

et al. 2007

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“…For instance, physical loss of 16q, the most frequent genomic change observed in grade I tumours, is exceedingly infrequent in high-grade breast carcinomas [2,12,13,33]. Although loss of 16q is observed in a subset of grade III carcinomas, it has recently been shown to occur by a distinct mechanism (LOH in combination with mitotic recombination) [34].…”

Section: Invasive and In Situ Breast Carcinomasmentioning

confidence: 99%

Molecular evolution of breast cancer

Simpson

Reis‐Filho

Gale

et al. 2005

The Journal of Pathology

449

378

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Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low-and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.

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“…Loss of chromosomal material on the long arm of chromosome 16 was observed frequently in several cancers, including breast, prostate, ovarian and fallopian tubes cancer. 43,44 The function of TOX3 is unknown, but a putative high-mobility group motif suggests that it might act as a transcription factor or is involved in the alteration of the chromatin structure. 45 In conclusion, using a Chinese and a German population-based casecontrol study, SNPs in the Chinese and German population associated with breast cancer were identified.…”

Section: Discussionmentioning

confidence: 99%

Comparison of genetic variation of breast cancer susceptibility genes in Chinese and German populations

et al. 2013

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Genome-wide association studies (GWAS) identified several genetic risk factors for breast cancer, however, most of them were validated among women of European ancestry. This study examined single-nucleotide polymorphisms (SNPs) contributing to breast cancer in Chinese (984 cases and 2206 controls) and German (311 cases and 960 controls) populations. Eighteen SNPs significantly associated with breast cancer, previously identified in GWAS were genotyped. Twelve SNPs passed quality control and were subjected to statistical analysis. Seven SNPs were confirmed to be significantly associated with breast cancer in the Chinese population, reflecting three independent loci (ESR1, FGFR2, TOX3) and five of these were also confirmed in the German population. The strongest association was identified for rs2046210 in the Chinese (odds ratio (OR) ¼ 1.42, 95% confidence interval (CI) ¼ 1.28-1.59, P ¼ 1.9 Â 10 À10 ) and rs3803662 in the German population (OR ¼ 1.43, 95% CI ¼ 1.17-1.74, P ¼ 4.01 Â 10 À4 ), located upstream of the ESR1 and TOX3 gene, respectively. For the first time, rs3757318 at 6q25.1, located next to the gene encoding estrogen receptor a (ESR1) was found to be strongly associated with breast cancer (OR ¼ 1.33, 95% CI ¼ 1.18-1.49, P ¼ 1.94 Â 10 À6 ) in the Chinese population. The frequency of this variant was markedly lower in the German population and the association was not significant. Despite the genetic differences, essentially the same risk loci were identified in the Chinese and the German populations. Our study suggested the existence of common genetic factors as well as disease susceptibility differences for breast cancer in both populations and highlighted the importance of performing comparison analyses for disease susceptibility within ethnic populations. INTRODUCTIONBreast cancer is the most common cancer in women and a common cause of cancer-related death worldwide. 1 The risk of breast cancer is determined by both genetic and lifestyle factors. 2 The variation in breast cancer incidence between populations can be explained in part by differences in lifestyle factors, such as reproductive patterns or diet. However, there is substantial variation within a population that seems to be determined by inherited genetic risk factors, possibly modified by external factors. 3 The overall contribution of inherited genes to the development of a disease can be quantified by the familial aggregation of the disease. Epidemiological studies have shown that breast cancer is about twice as common in first-degree relatives of women with the disease than in the general population, reflecting the inheritable component of the disease. 4 A considerably higher risk in monozygotic twins of affected relatives than in dizygotic twins has been demonstrated in twin studies, suggesting that the familial aggregation is largely determined by inheritable rather than environmental risk factors. 5,6 GWAS plus previous linkage and candidate gene association studies have identified many susceptibility genes, the most prominent being

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Different mechanisms of chromosome 16 loss of heterozygosity in well‐ versus poorly differentiated ductal breast cancer

Cited by 53 publications

References 30 publications

Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

Molecular evolution of breast cancer

Comparison of genetic variation of breast cancer susceptibility genes in Chinese and German populations

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