Genotype/Phenotype Correlations in Patients with Hereditary Breast Cancer

Wittersheim, Maike; Büttner, Reinhard; Markiefka, Birgid

doi:10.1159/000380900

Cited by 17 publications

(10 citation statements)

References 53 publications

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“…Invasive LBC is the second most common histological type of breast cancer, accounting for 5%–15% of invasive breast cancers, and is one of the few histological subtypes harbouring a distinct genetic alteration that is associated with a specific phenotype 62. Indeed, around 90% of invasive LBC display E-cadherin loss, either at the DNA, mRNA or protein level and, in the few tumours preserving expression, E-cadherin integrity is nonetheless impaired 63 64.…”

Section: Introductionmentioning

confidence: 99%

Clinical spectrum and pleiotropic nature ofCDH1germline mutations

et al. 2019

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CDH1 encodes E-cadherin, a key protein in adherens junctions. Given that E-cadherin is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, it is no surprise that deleterious effects arise from its loss of function. E-cadherin is recognised as a tumour suppressor gene, and it is well established that CDH1 genetic alterations cause diffuse gastric cancer and lobular breast cancer—the foremost manifestations of the hereditary diffuse gastric cancer syndrome. However, in the last decade, evidence has emerged demonstrating that CDH1 mutations can be associated with lobular breast cancer and/or several congenital abnormalities, without any personal or family history of diffuse gastric cancer. To date, no genotype–phenotype correlations have been observed. Remarkably, there are reports of mutations affecting the same nucleotide but inducing distinct clinical outcomes. In this review, we bring together a comprehensive analysis of CDH1-associated disorders and germline alterations found in each trait, providing important insights into the biological mechanisms underlying E-cadherin’s pleiotropic effects. Ultimately, this knowledge will impact genetic counselling and will be relevant to the assessment of risk of cancer development or congenital malformations in CDH1 mutation carriers.

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Section: Introductionmentioning

confidence: 99%

Clinical spectrum and pleiotropic nature ofCDH1germline mutations

et al. 2019

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“…These features can also help identify tumors more likely to harbor BRCA1/2 mutations. For example, breast cancers arising in gBRCA1 carriers prototypically are of high grade and of the basal-like subtype with more frequent necrosis and lymphocytic infiltration (16,17). BRCA1-associated high-grade serous tubo-ovarian carcinoma (HGSOC) shows more frequent (partial) Solid, pseudoEndometrioid, and/or Transitional morphology (SET morphology), which is distinctly different from the prototypical papillary and infiltrative growth generally encountered in sporadic HGSOC.…”

Section: Introductionmentioning

confidence: 99%

“…[18][19][20]. On a molecular level, gBRCA-associated breast cancers and OCs share similar somatic copy-number profiles [somatic copy-number alteration (SCNA)-high] and frequent TP53 mutations (16)(17)(18)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Germline BRCA-Associated Endometrial Carcinoma Is a Distinct Clinicopathologic Entity

Jonge

Ritterhouse

Kroon

et al. 2019

Clinical Cancer Research

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Purpose: Whether endometrial carcinoma (EC) should be considered part of the gBRCA1/2-associated hereditary breast and ovarian cancer (HBOC) syndrome is topic of debate. We sought to assess whether ECs occurring in gBRCA carriers are enriched for clinicopathologic and molecular characteristics, thereby supporting a causal relationship. Experimental Design: Thirty-eight gBRCA carriers that developed EC were selected from the nationwide cohort study on hereditary breast and ovarian cancer in the Netherlands (HEBON), and these were supplemented with four institutional cases. Tumor tissue was retrieved via PALGA (Dutch Pathology Registry). Nineteen morphologic features were scored and histotype was determined by three expert gynecologic pathologists, blinded for molecular analyses (UCM-OncoPlus Assay including 1213 genes). ECs with LOH of the gBRCA-wild-type allele (gBRCA/LOHpos) were defined "gBRCA-associated," those without LOH (gBRCA/LOHneg) were defined "sporadic." Results: LOH could be assessed for 40 ECs (30 gBRCA1, 10 gBRCA2), of which 60% were gBRCA/LOHpos. gBRCA/LOHpos ECs were more frequently of nonendometrioid (58%, P ¼ 0.001) and grade 3 histology (79%, P < 0.001). All but two were in the TP53-mutated TCGA-subgroup (91.7%, P < 0.001). In contrast, gBRCA/LOHneg ECs were mainly grade 1 endometrioid EC (94%) and showed a more heterogeneous distribution of TCGA-molecular subgroups: POLE-mutated (6.3%), MSI-high (25%), NSMP (62.5%), and TP53-mutated (6.3%). Conclusions: We provide novel evidence in favor of EC being part of the gBRCA-associated HBOC-syndrome. gBRCAassociated ECs are enriched for EC subtypes associated with unfavorable clinical outcome. These findings have profound therapeutic consequences as these patients may benefit from treatment strategies such as PARP inhibitors. In addition, it should influence counseling and surveillance of gBRCA carriers.

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“…These studies include evaluating the association of genotype and phenotype with the response to treatment and type of clinicopathologic features of patients. Such studies investigated the role of mutations, gene expressions, or epigenetic changes in various subgroups of affected people (3,4).…”

Section: Introductionmentioning

confidence: 99%

Molecular studies of breast cancer in Iran: A Systematic Review

Esmaeili

Eslami-S

Drayani

et al. 2020

Preprint

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Background: The present study aimed to review the existing cellular and molecular research systematically carried out in the field of breast cancer in Iran. This study was part of a big project, which evaluated a variety of studies conducted on breast cancer in Iran.Methods: All molecular articles about breast cancer in Iran which were published from January 2005 to October 21, 2015 were included. English and Persian databases consisted of Web of Science, PubMed, Scopus, Scientific Information Database (SID) and IranMedex. Finally of 3331 abstracts, a total of 379 articles, including 219 English and 160 Persian papers related to molecular studies were included in this study.Results: After initial evaluations, 240 studies were included. Molecular studies conducted in Iran were divided into four main groups based on their focus. They evaluated breast cancer susceptibility genes, Prognosis and clinicopathologic features of the patients, compounds with therapeutic properties, and diagnosis. Moreover, ethical statements in manuscripts were investigated.Conclusions: Result of this review showed that most of the researches in Iran categorize to 4 main subjects. The majority of the studies in Iran were conducted sporadically and with small sample sizes. Stronger studies would require the development of more biological banks and execution of multicenter comprehensive projects defined with orientation to main problems of Breast Cancer patients in the country.

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Genotype/Phenotype Correlations in Patients with Hereditary Breast Cancer

Cited by 17 publications

References 53 publications

Clinical spectrum and pleiotropic nature ofCDH1germline mutations

Clinical spectrum and pleiotropic nature ofCDH1germline mutations

Germline BRCA-Associated Endometrial Carcinoma Is a Distinct Clinicopathologic Entity

Molecular studies of breast cancer in Iran: A Systematic Review

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