Germline mutations of the E‐cadherin gene in families with inherited invasive lobular breast carcinoma but no diffuse gastric cancer

Xie, Ze Ming; Li, Lai Sheng; Laquet, Claire; Penault‐Llorca, Frédérique; Uhrhammer, Nancy; Xie, Xiao; Bignon, Yves Jean

doi:10.1002/cncr.25876

Cited by 62 publications

(39 citation statements)

References 19 publications

(28 reference statements)

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“…The CDH1 mutations in the 22 ILC cases included in this study were all unique and involved point mutations in 20 (91%) cases and splice site mutations/deletions in 2 (9%) cases. In triple-negative IDC of the breast, loss of E-cadherin expression has been linked to adverse clinical outcome (23). Finally, neither CDH1 mutation nor loss of E-cadherin function by other mechanisms, are considered targets for anticancer therapy at this time (24).…”

Section: Discussionmentioning

confidence: 99%

Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency ofHER2(ERBB2) Gene Mutations

Ross

Wang

Sheehan

et al. 2013

Clinical Cancer Research

124

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Purpose: We queried whether comprehensive genomic profiling using a next-generation sequencingbased assay could identify novel and unanticipated targets of therapy for patients with relapsed invasive lobular carcinoma (ILC).Experimental Design: DNA sequencing (Illumina HiSeq 2000) was conducted for 3,320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor-ligated, hybridization-captured libraries using DNA isolated from formalin-fixed paraffin-embedded sections from 22 histologically verified ILC.Results: A total of 75 genomic alterations were identified with an average of 3.4 alterations per tumor (range, 1-6), of which 35 were actionable for an average of 1.59 actionable alterations per patient (range, 0-3). Nineteen of 22 (86%) of the ILC samples harbored at least one actionable alteration. Six (27%) cases featured alterations in ERRB2 including 4 (18%) with ERBB2 mutation, 1 (5%) with an ERBB2 gene fusion, and 1 (5%) with an ERBB2 copy number gain (amplification). The enrichment of ERBB2 mutations/fusion in CDH1-mutated ILC (5 of 22, 23%) compared with the 5 ERBB2 mutations in a series of 286 non-CDH1-mutated breast cancers from which the ILC cases were obtained (5 of 286, 2%) was significant (P ¼ 0.0006).Conclusions: Comprehensive genomic profiling of relapsed CDH1-mutated ILC revealed actionable genomic alterations in 86% of cases, featured a high incidence of ERBB2 alterations, and can reveal actionable alterations that can inform treatment decisions for patients with ILC.

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Section: Discussionmentioning

confidence: 99%

Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency ofHER2(ERBB2) Gene Mutations

Ross

Wang

Sheehan

et al. 2013

Clinical Cancer Research

124

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“…Carriers of CDH1 mutations face a 40-54% lifetime risk of developing BC 85 . Without a family history of hereditary diffuse gastric carcinoma, early-onset, and frequently bilateral BC, seems to be the highest risk factors for a mutation carrier [86][87][88][89] .…”

Section: Cdh1mentioning

confidence: 99%

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Gómez-Flores-Ramos¹,

Castro-Sánchez

Peña-Curiel

et al. 2017

RIC

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Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

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“…The vast majority of families with truncating CDH1 mutations have a history of HDGC; however, at least one other family has been reported to only have a family history of invasive lobular breast cancer, but not HDGC (Xie et al. 2011). It is unclear whether this phenotype reflects a new genotype/phenotype correlation or just an expansion of the general truncating CDH1 mutation phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…2008; Xie et al. 2011). However, prophylactic total gastrectomy is currently recommended for CDH1 mutation carriers due to reported high penetrance (van der Post et al.…”

Section: Introductionmentioning

confidence: 99%

Panel testing reveals nonsense and missense CDH1 mutations in families without hereditary diffuse gastric cancer

Huynh

Laukaitis

2016

Molec Gen & Gen Med

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BackgroundThe reported penetrance of germline CDH1 mutations is high in families with hereditary diffuse gastric cancer (HDGC). Men and women have a 70% and 56%, respectively, cumulative risk of developing diffuse gastric cancer by age 80. Women additionally have a 42% cumulative risk of developing breast cancer. Due to the high penetrance of these mutations, prophylactic total gastrectomy is currently recommended for CDH1 mutation carriers. However, whether everyone with a CDH1 gene mutation is at risk for HDGC is not clear.MethodsMutation identification was performed by next‐generation sequencing. Mutations and variant status was confirmed by Sanger sequencing in 11 family members.ResultsWe present two families with pathogenic CDH1 mutations. The first family carries a novel truncating, nonsense CDH1 mutation that we were able to trace for three generations, but reports no family history of diffuse gastric cancer. The occurrence of cancer in this family deviates significantly from the expectation for HDGC. The proband from the second family presents with breast cancer and carries a previously reported pathogenic CDH1 mutation, but also reports no family history of diffuse gastric cancer.ConclusionsOur study demonstrates the need for further analysis of CDH1 mutation penetrance in order to better counsel asymptomatic CDH1 mutation carriers on preventative measures and general care.

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Germline mutations of the E‐cadherin gene in families with inherited invasive lobular breast carcinoma but no diffuse gastric cancer

Cited by 62 publications

References 19 publications

Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency ofHER2(ERBB2) Gene Mutations

Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency ofHER2(ERBB2) Gene Mutations

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Panel testing reveals nonsense and missense CDH1 mutations in families without hereditary diffuse gastric cancer

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