Patterns of Chromosomal Alterations in Breast Ductal Carcinoma <b>
                     <i>In situ</i>
                  </b>

Hwang, E. Shelley; DeVries, Sandy; Chew, Karen; Moore, Dan H.; Kerlikowske, Karla; Thor, Ann D.; Ljung, Britt–Marie; Waldman, Frederic M.

doi:10.1158/1078-0432.ccr-04-0165

Cited by 118 publications

(121 citation statements)

References 34 publications

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“…Comparative genomic hybridization analysis of breast DCIS and IDC found no significant difference in the number of chromosomal abnormalities, although the frequency of a few specific changes varied in high grade versus low grade DCIS and between DCIS and concurrent IDC. 9 A more recent study confirmed that DCIS is genetically advanced. Allelic imbalance of 52 microsatellite markers of chromosomal regions commonly lost in breast cancer increased significantly between atypical ductal hyperplasia and DCIS but not between DCIS and IDC.…”

mentioning

confidence: 95%

Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts

Tait

Pauley

Santner

et al. 2007

Intl Journal of Cancer

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cells form comedo type ductal carcinoma in situ in immune-deficient mice before forming invasive ductal carcinoma. As the lesions mature, both stromal and epithelial cells undergo phenotypic changes detected by immunohistochemistry. Myofibroblasts are present before the formation of carcinoma in situ and after development of invasive carcinoma. MCF10DCIS. com lesions develop a myoepithelial layer prior to exhibiting a basement membrane surrounding the ductal mass. TGFb1 is initially expressed by the epithelial cells but is expressed by stroma in invasive carcinoma. Stromal derived factor-1 is detected in epithelial cells in early carcinoma in situ but is produced in stromal cells in invasive carcinoma. The receptor CXCR4 is expressed by epithelial cells in the xenografts at all times, as is the hepatocyte growth factor receptor c-met. MCF10DCIS.com xenografts illustrate the dynamic interplay of epithelium and stroma in the development of carcinoma in situ and subsequent invasive carcinoma. Although the phenotype of the epithelial cells may be dependent upon the stroma, the malignant epithelium induces the development of the stroma necessary for progression to the invasive stage. ' 2007 Wiley-Liss, Inc.Key words: breast cancer; carcinoma in situ; MCF10DCIS.com; progression; stroma; xenograft The natural history of cancer is thought to involve multiple sequential genetic changes including mutations, loss of heterozygosity and amplification of gene copy number as well as epigenetic changes such as hypermethylation of promoter regions. In many epithelial cancers a series of abnormal histologic changes can be identified and associated with increased risk of progressing to malignant disease. It has been assumed that each stage accumulates additional genetic anomalies. The first recognized lesion with increased risk for breast cancer is hyperplasia ( a 4-fold increased risk for atypical ductal hyperplasia) but genetic anomalies are rare. ErbB2 is rarely detected in benign lesions. 1-3 However, overexpression of erbB2 is frequent in DCIS and IDC. Studies of mixed lesions, containing both in situ and invasive components, invariably report that the 2 components express erbB2 coordinately. 4-6 A similar pattern occurs for cyclin D1 expression; rare in benign hyperplastic lesions but frequent in both DCIS and IDC and expressed coordinately in both in situ and invasive components of mixed lesions. 7,8 Recent studies suggest that nearly all genetic alterations have occurred by the time of DCIS formation. Comparative genomic hybridization analysis of breast DCIS and IDC found no significant difference in the number of chromosomal abnormalities, although the frequency of a few specific changes varied in high grade versus low grade DCIS and between DCIS and concurrent IDC. 9 A more recent study confirmed that DCIS is genetically advanced. Allelic imbalance of 52 microsatellite markers of chromosomal regions commonly lost in breast cancer increased significantly between atypical ductal hyperplasia and DCIS but not between DCIS an...

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mentioning

confidence: 95%

Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts

Tait

Pauley

Santner

et al. 2007

Intl Journal of Cancer

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“…DCIS has long been known to be heterogeneous in its morphologic features, presentation, and clinical behavior. The emergence of genomic and gene expression profiling has established that DCIS is heterogeneous at a level of molecular complexity that is comparable with or perhaps greater than that of invasive disease (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Although certainly less studied, the heterogeneity observed in the microenvironment surrounding individual premalignant lesions may also be a critical determinant of their future behavior.…”

Section: Introductionmentioning

confidence: 99%

Premalignant Breast Neoplasia: A Paradigm of Interlesional and Intralesional Molecular Heterogeneity and Its Biological and Clinical Ramifications

Berman

Gauthier

Tlsty

2010

Cancer Prevention Research

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As is well established in invasive breast disease, it is becoming increasingly clear that molecular heterogeneity, both between and within lesions, is a prevalent, distinct phenotype of premalignant lesions of the breast. Key pathways of tumorigenesis modulate critical features of premalignant lesions such as proliferation, differentiation, stress response, and even the generation of diversity. Current studies show that evaluation of these lesions may provide clinically useful information on future tumor formation as well as biological insights into the origin and functional significance of this distinct phenotype. Cancer Prev Res; 3(5); 579-87. ©2010 AACR.

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“…Comparative genomic hybridization (CGH) also shows frequent losses of distal 8p in breast, colorectal, prostate, bladder and other cancers (e.g. Davidson et al, 2000;AbdelRahman et al, 2001;Karan et al, 2003;Hurst et al, 2004;Hwang et al, 2004), and more recently array CGH has begun to provide more detail of these losses (e.g. Paris et al, 2003;Douglas et al, 2004;Hurst et al, 2004;Nakao et al, 2004;Garcia et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

et al. 2006

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The short arm of chromosome 8, 8p, is often rearranged in carcinomas, typically showing distal loss by unbalanced translocation. We analysed 8p rearrangements in 48 breast, pancreatic and colon cancer cell lines by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization, with a tiling path of 0.2 Mb resolution over 8p12 and 1 Mb resolution over chromosome 8. Selected breast lines (MDA-MB-134, MDA-MB-175, MDA-MB-361, T-47D and ZR-75-1) were analysed further. Most cell lines showed loss of 8p distal to a break that was between 31 Mb (5 0 to NRG1) and the centromere, but the translocations were accompanied by variable amplifications, deletions and inversions proximal to this break. The 8p12 translocation in T-47D was flanked by an inversion of 4 Mb, with a 100 kb deletion at the proximal end. The dicentric t(8;11) in ZR-75-1 carries multiple rearrangements including interstitial deletions, a triplicated translocation junction between NRG1 and a fragment of 11q (unconnected to CCND1), and two separate amplifications, of FGFR1 and CCND1 . We conclude that if there is a tumour suppressor gene on 8p it may be near 31 Mb, for example WRN; but the complexity of 8p rearrangements suggests that they target various genes proximal to 31 Mb including NRG1 and the amplicon centred around ZNF703/FLJ14299.

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Patterns of Chromosomal Alterations in Breast Ductal Carcinoma In situ

Abstract: ABSTRACT

Cited by 118 publications

References 34 publications

Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts

Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts

Premalignant Breast Neoplasia: A Paradigm of Interlesional and Intralesional Molecular Heterogeneity and Its Biological and Clinical Ramifications

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

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