Cytogenetic abnormalities in an in situ ductal carcinoma and five prophylactically removed breasts from members of a family with hereditary breast cancer

Teixeira, Manuel R.; Pandis, Nikos; Gerdes, Anne-Marie; Dietrich, Claudia U.; Bardi, Georgia; Andersen, Johan A.; Graversen, H. P.; Mitelman, Felix; Heim, Sverre

doi:10.1016/0165-4608(96)85312-x

Cited by 11 publications

(19 citation statements)

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“…A morphologic continuum exists from proliferative breast disease to carcinoma in situ and eventually to invasive tumors with a potential to metastasize, but the evidence that the common breast cancers actually proceed through all these stages is mostly circumstantial (Ponté n et al, 1990;Lennington et al, 1994;Page et al, 1995). Some of the primary cytogenetic changes characteristic of breast carcinomas have also occasionally been detected in the epithelial component of benign breast proliferations and in mammary tissue predisposed to carcinogenesis Dietrich et al, 1995;Teixeira et al, 1996a). Although this finding may substantiate their role as pathogenetically important, early events in breast carcinogenesis, it must also mean that although these chromosome changes confer upon the cells harboring them a proliferative advantage over their neighbors, they are not sufficient alone to induce a malignant phenotype.…”

Section: Karyotypic Model Of Breast Carcinogenesismentioning

confidence: 99%

“…The original data on which this review is based have been published from 1992 to 2001 (Pandis et al, 1992b(Pandis et al, , 1993a(Pandis et al, ,b, 1994b(Pandis et al, , 1995a(Pandis et al, ,b, 1998Teixeira et al, 1994Teixeira et al, , 1995Teixeira et al, , 1996aTeixeira et al, ,b, 1997Teixeira et al, , 1998aTeixeira et al, ,b, 2001Adeyinka et al, , 1997Adeyinka et al, , 1999aAdeyinka et al, ,b, 2000Tsarouha et al, 1999). Clonal chromosome abnormalities have been detected in 322 breast carcinoma samples from 256 patients with this disease, which enabled us also to compare cytogenetically multiple intratumor samples, multiple ipsilateral and bilateral breast carcinomas, and primary tumors and their metastases.…”

Section: Cytogenetic Characterization Of Breast Carcinomasmentioning

confidence: 99%

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Cytogenetic clues to breast carcinogenesis

Teixeira

Pandis

Heim

2001

Genes Chromosomes & Cancer

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The somatic mutation theory of cancer maintains that tumorigenesis is driven by genetic alterations, many of which are visible cytogenetically. We have examined breast cancer by chromosome banding analysis after short-term culturing of tumor cells and here review our findings in 322 karyotypically abnormal samples obtained since 1992 from 256 patients. The screening capabilities of this technique enabled us to identify several cytogenetic subgroups of breast cancer, to study the intratumor heterogeneity of breast carcinomas, and to compare primary tumors with their metastases. Using chromosome abnormalities as clonality markers, we could determine on an individual basis when multiple, ipsilateral or bilateral breast, tumors were independent de novo carcinomas and when they resulted from the spreading of a single malignant clone within one breast or from one breast to the other. The distribution of chromosomal breakpoints and genomic gains and losses is clearly nonrandom in breast cancer, something that can guide further investigations using molecular methods. Based on the total dataset, we propose a multipathway model of mammary carcinogenesis that takes into consideration the genetic heterogeneity revealed by the karyotypic findings and review the karyotypic-pathologic correlations and the possible clinical applications of the cytogenetic knowledge.

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Section: Karyotypic Model Of Breast Carcinogenesismentioning

confidence: 99%

Section: Cytogenetic Characterization Of Breast Carcinomasmentioning

confidence: 99%

Cytogenetic clues to breast carcinogenesis

Teixeira

Pandis

Heim

2001

Genes Chromosomes & Cancer

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“…This intratumor clonal heterogeneity has been reported for a wide range of malignancies, ranging from hematopoietic cancers to different types of solid tumors (3)(4)(5)(6)(7). Among others, the existence of clonal heterogeneity was documented in breast carcinomas using a variety of molecular and cytological techniques, both within primary tumors (8)(9)(10) and between matched primary tumors and distant metastases (9,11). It is widely hypothesized that intratumor clonal heterogeneity underlies therapeutic resistance (2,3).…”

Section: Introductionmentioning

confidence: 99%

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype

Park¹,

Gönen²,

Kim³

et al. 2010

J. Clin. Invest.

306

273

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Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem celllike and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments. IntroductionWith rare exceptions, human malignancies are thought to originate from a single cell, yet by the time of diagnosis, most tumors display startling heterogeneity in cell morphology, proliferation rates, angiogenic and metastatic potential, and expression of cell surface molecules (1, 2). This heterogeneity is in part caused by epigenetic and morphological plasticity, including variability for stem cell-like and more-differentiated cell characteristics, but there is also strong evidence for the existence of genetically distinct clones within the same tumor. This intratumor clonal heterogeneity has been reported for a wide range of malignancies, ranging from hematopoietic cancers to different types of solid tumors (3-7). Among others, the existence of clonal heterogeneity was documented in breast carcinomas using a variety of molecular and cytological techniques, both within primary tumors (8-10) and between matched primary tumors and distant metastases (9, 11). It is widely hypothesized that intratumor clonal heterogeneity underlies therapeutic resistance (2, 3). Supporting this hypothesis, the extent of the intratumor clonal heterogeneity measured based on FISH and TP53 and CDKN2A mutation data was associated with higher risk of tumor progression in esophageal carcinoma (4).Despite the importance of intratumor genetic heterogeneity in tumor progression and therapeutic resistance, currently there are no established methods for the quantitative assessment of intratumor diversity at the cellular level that could be used as a biomarker

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“…LOH was also detected in hyperplasias (usual ductal hyperplasia and atypical ductal hyperplasia) from both cancerous and noncancerous breasts (6,7). In addition, two recent studies have also shown cytogenetic abnormalities in prophylactic mastectomy specimens characterized by hyperplasia, without atypia, from patients with a positive family history of breast cancer (but of unknown BRCA status) (8,9). Deletions of 3pl4 have been observed in benign proliferative breast disease (9,10) and one report has shown that the FHIT gene was homozygously deleted in two cases of benign proliferative breast disease associated with 3pl4 cytogenetic rearrangements and familial breast cancer (11).…”

Section: Introductionmentioning

confidence: 85%

Characterization of Early Genomic Changes in Mammary Glands in High Risk Women

Haddad¹

2002

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Cytogenetic abnormalities in an in situ ductal carcinoma and five prophylactically removed breasts from members of a family with hereditary breast cancer

Cited by 11 publications

References 0 publications

Cytogenetic clues to breast carcinogenesis

Cytogenetic clues to breast carcinogenesis

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype

Characterization of Early Genomic Changes in Mammary Glands in High Risk Women

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