Characterization of a novel founder <i><scp>MSH6</scp></i> mutation causing Lynch syndrome in the French Canadian population

Castellsagué, Ester; Liu, J.; Volenik, Alexandra; Giroux, Sylvie; Gagné, Richard; Maranda, Bruno; Roussel-Jobin, A.; Latreille, Jean; Laframboise, Rachel; Palma, Laura; Kasprzak, Lidia; Marcus, Victoria; Bréguet, Magali; Nolet, Serge; El-Haffaf, Zaki; Australie, K; Gologan, Adrian; Aleynikova, Olga; Oros-Klein, K.; Greenwood, Celia M.T.; Mes-Masson, Anne-Marie; Provencher, Diane; Tischkowitz, Marc; Chong, George; Rousseau, François; Foulkes, William D.

doi:10.1111/cge.12526

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…Further analysis of other members of our cancer family showed only one of five other carriers was affected by BC (unpublished data). This case is from the French Canadian population and carries a pathogenic variant in BRCA2 c.8537_8538delAG; p.Glu2846GlyfsTer22 known to be a founder pathogenic variant as reported by our group and others [84][85][86][87][88][89][90][91][92][93].…”

Section: Carriers Of a Bard1 Variant And A Pathogenic Variant In A Knsupporting

confidence: 52%

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Alenezi

Fierheller

Recio

et al. 2020

Genes

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Soon after the discovery of BRCA1 and BRCA2 over 20 years ago, it became apparent that not all hereditary breast and/or ovarian cancer syndrome families were explained by germline variants in these cancer predisposing genes, suggesting that other such genes have yet to be discovered. BRCA1-associated ring domain (BARD1), a direct interacting partner of BRCA1, was one of the earliest candidates investigated. Sequencing analyses revealed that potentially pathogenic BARD1 variants likely conferred a low–moderate risk to hereditary breast cancer, but this association is inconsistent. Here, we review studies of BARD1 as a cancer predisposing gene and illustrate the challenge of discovering additional cancer risk genes for hereditary breast and/or ovarian cancer. We selected peer reviewed research articles that focused on three themes: (i) sequence analyses of BARD1 to identify potentially pathogenic germline variants in adult hereditary cancer syndromes; (ii) biological assays of BARD1 variants to assess their effect on protein function; and (iii) association studies of BARD1 variants in family-based and case-control study groups to assess cancer risk. In conclusion, BARD1 is likely to be a low–moderate penetrance breast cancer risk gene.

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Section: Carriers Of a Bard1 Variant And A Pathogenic Variant In A Knsupporting

confidence: 52%

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Alenezi

Fierheller

Recio

et al. 2020

Genes

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“…By contrast, we found that endometrioid ovarian cancer was strongly associated with endometrial cancer in the two-way comparison, which could imply association with HNPCC syndrome related to MSH6 mutations in patients with the endometrioid and clear cell ovarian carcinomas 25 . Carriers with MSH6 germline mutations appear to have a high risk of endometrial cancer but low risk of colorectal cancer 26 .…”

Section: Discussionmentioning

confidence: 99%

Familial Ovarian Cancer Clusters with Other Cancers

Zheng

Kanerva

et al. 2018

Sci Rep

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Familial risk of ovarian cancer is well-established but whether ovarian cancer clusters with other cancers and the clusters differ by histology remains uncertain. Using data from the Swedish Family-Cancer Database, we explored familial associations of ovarian cancer with other cancers with a novel approach; relative risk for (histology-specific) ovarian cancer was estimated in families with patients affected by other cancers, and conversely, risks for other cancers in families with (histology-specific) ovarian cancer patients. Eight discordant cancers were associated with ovarian cancer risk, of which family history of breast cancer showed a dose-response (P-trend <0.0001). Conversely, risks of eight types of cancer increased in families with ovarian cancer patients, and dose-responses were shown for risks of liver (P-trend = 0.0083) and breast cancers (P-trend <0.0001) and cancer of unknown primary (P-trend = 0.0157). Some cancers were only associated with histology-specific ovarian cancers, e.g. endometrial cancer was only associated with endometrioid type but with highest significance. Novel associations with virus-linked cancers of the nose and male and female genitals were found. The results suggest that ovarian cancer shares susceptibility with a number of other cancers. This might alert genetic counselors and challenge approaches for gene and gene-environment identification.

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“…(0.092%; 1:1087), and PMS2 p.P246Cfs*3 (0.234%; 1:427) . Other research has demonstrated that the MSH6 p.Q4* founder mutation is particularly prevalent in French Canadian individuals, with an estimated carrier frequency of 0.249% (1:402), and haplotype analysis suggests that the mutation arose in a common ancestor from 430 to 656 years ago . Although their population prevalence is not well understood, founder mutations in MSH2 (c.1906G>C, p.A636P) and MSH6 (c.3959_3962delCAAG and c.3984_3987dupGTCA) appear to account for the majority of Lynch syndrome cases in individuals of Ashkenazi Jewish ancestry .…”

Section: Epidemiology Of Lynch Syndromementioning

confidence: 99%

Recent progress in Lynch syndrome and other familial colorectal cancer syndromes

Boland

Yurgelun

Boland

2018

CA A Cancer J Clinicians

136

106

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The current understanding of familial colorectal cancer was limited to descriptions of affected pedigrees until the early 1990s. A series of landscape-altering discoveries revealed that there were distinct forms of familial cancer, and most were related to genes previously not known to be involved in human disease. This review largely focuses on advances in our understanding of Lynch syndrome because of the unique relationship of this disease to defective DNA mismatch repair and the clinical implications this has for diagnostics, prevention, and therapy. Recent advances have occurred in our understanding of the epidemiology of this disease, and the advent of broad genetic panels has altered the approach to germline and somatic diagnoses for all of the familial colorectal cancer syndromes. Important advances have been made toward a more complete mechanistic understanding of the pathogenesis of neoplasia in the setting of Lynch syndrome, and these advances have important implications for prevention. Finally, paradigm-shifting approaches to treatment of Lynch-syndrome and related tumors have occurred through the development of immune checkpoint therapies for hypermutated cancers. CA Cancer J Clin 2018;68:217-231. © 2018 American Cancer Society.

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Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population

Cited by 15 publications

References 23 publications

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Familial Ovarian Cancer Clusters with Other Cancers

Recent progress in Lynch syndrome and other familial colorectal cancer syndromes

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