Different CHEK2 germline mutations are associated with distinct immunophenotypic molecular subtypes of breast cancer

Domagała, Paweł; Wokołorczyk, Dominika; Cybulski, Cezary; Huzarski, Tomasz; Lubiński, Jan; Domagała, W

doi:10.1007/s10549-011-1635-7

Cited by 35 publications

(36 citation statements)

References 43 publications

(68 reference statements)

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“…After screening, we excluded articles in which CHEK2 I157T was not a studied variant or in which CHEK2 I157T was studied but not in breast cancer. 21 studies (Allinen et al, 2001;Schutte et al, 2003;Cybulski et al, 2004;Dufault et al, 2004;Kilpivaara et al, 2004;Bogdanova et al, 2005;Górski et al, 2005;Cybulski et al, 2006;Nevanlinna et al, 2006;Meyer et al, 2007;Cybulski et al, 2008;Falchetti et al, 2008;Novak et al, 2008;Kaufman et al, 2008;Kleib et al, 2008;Serrano-Fernandez et al, 2009;Scharrer et al, 2010;Cybulski et al, 2011;Domagala et al, 2011) examined the association between CHEK2 variants and breast cancer susceptibility. We then excluded non-casecontrolled, data duplicating, review, new gene variant, and male breast cancer studies.…”

Section: Resultsmentioning

confidence: 99%

“…In these studies, we identified thirteen studies of unselected breast cancer (Allinen et al, 2001;Schutte et al, 2003;Cybulski et al, 2004;Kilpivaara et al, 2004;Bogdanova et al, 2005;Górski et al, 2005;Huzarski et al, 2005;Cybulski et al, 2008;Kleib et al, 2008;Serrano-Fernandez et al, 2009;Scharrer Cybulski et al, 2011;Domagala et al, 2011) and three of lobular breast cancer Cybulski et al, 2011;Domagala et al, 2011). Characteristics of included studies are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Cases with both truncating and missense (I157T) variants were available in two studies (Cybulski et al, 2007;Domagala et al, 2011).…”

Section: Data Abstractionmentioning

confidence: 99%

See 2 more Smart Citations

The CHEK2 I157T Variant and Breast Cancer Susceptibility: A Systematic Review and Meta-analysis

Liu¹,

Wang²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The CHEK2 I157T Variant and Breast Cancer Susceptibility: A Systematic Review and Meta-analysis

Liu¹,

Wang²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…CHEK2 (cell-cycle checkpoint kinase) gene is a strong candidate gene for a low risk breast cancer susceptibility on chromosome 22q12.1 (Bartek et al, 2001;Einarsdottir et al, 2006). The protein product of this gene functions as a serine/threonine protein kinase that phosphorylates various substrates such as BRCA1, p53, Cdc25 family proteins (Domagala et al, 2012) and also, it regulates the tumour suppressor functions of these proteins. In response to DNA double-strand breaks or replicative stress, CHEK2 activates cell-cycle checkpoints for promoting cell-cycle arrest and increases DNA repair efficiency.…”

Section: Identification Of a Novel Brca2 And Chek2 A-c-g-c Haplotype mentioning

confidence: 99%

“…In contrast, another common variant I157T results in the substitution of an isoleucine to a threonine. The protein product of an I157T missense variant is stable, but defective in its ability to bind BRCA1, p53 and Cdc25A (Domagala et al, 2012).…”

Section: Identification Of a Novel Brca2 And Chek2 A-c-g-c Haplotype mentioning

confidence: 99%

Identification of a Novel BRCA2 and CHEK2 A-C-G-C Haplotype in Turkish Patients Affected with Breast Cancer

Haytural

Yalçınkaya²,

Akan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. Methods: We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls. Results: We found significant associations in the analyses of CHEK2-1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls. The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2-Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (χ 2 =7.655; p=0.0057) in the patient group compared to controls. Conclusion: In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.

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Hereditary Breast Cancer Syndromes: Molecular Pathogenesis and Diagnostics

Vos

Groep

Wall

et al. 2015

Encyclopedia of Life Sciences

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Breast cancer is a major cause of morbidity and mortality worldwide. Approximately, 20% of breast cancer cases are due to a familial predisposition. Most of these familial breast cancers are due to mutations in well‐known genes linked to breast cancer, such as BRCA1 , BRCA2 , TP53 , CHEK2 , PTEN , CDH1 , STK11 / LKB1 , RAD50 , BRIP1 and PALB2 . Some of these cancers are, however, due to (a combination of) mutations in lower penetrance genes or some cancers show no relationship with known susceptibility genes. In this article, we describe the function of recently known breast cancer susceptibility genes, the molecular pathogenesis and the histopathology of these hereditary breast cancer syndromes. This may provide a better understanding and classification of hereditary breast cancer and may offer tools for better diagnosis and selection of patients sensitive to specific targeted therapies. Key Concepts Breast cancer is the most frequent cancer diagnosed in women worldwide. In 5–10% of total breast cancer cases, there is familial breast cancer susceptibility. Hereditary breast cancer is familial breast cancer with a clear Mendelian inheritance pattern. Breast cancer susceptibility genes can be divided into high‐, intermediate‐ and low‐risk genes, of which the high‐risk genes BRCA1 and BRCA2 are the best known. Breast cancer susceptibility genes mostly involve DNA repair mechanisms. The discovery of breast cancer susceptibility genes has improved our knowledge of breast carcinogenesis, including the morphological, immunohistochemical and molecular characterisation of familial breast cancer. Moreover, knowledge of the biological processes underlying familial breast cancer offers tools for cancer screening, prevention and management.

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Different CHEK2 germline mutations are associated with distinct immunophenotypic molecular subtypes of breast cancer

Cited by 35 publications

References 43 publications

The CHEK2 I157T Variant and Breast Cancer Susceptibility: A Systematic Review and Meta-analysis

The CHEK2 I157T Variant and Breast Cancer Susceptibility: A Systematic Review and Meta-analysis

Identification of a Novel BRCA2 and CHEK2 A-C-G-C Haplotype in Turkish Patients Affected with Breast Cancer

Hereditary Breast Cancer Syndromes: Molecular Pathogenesis and Diagnostics

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