Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma

Johansson, Peter; Nathan, Vaishnavi; Bourke, Lauren M.; Palmer, Jane M.; Zhang, Tongwu; Symmons, Judith; Howlie, Madeleine; Patch, Ann Marie; Read, Jazlyn; Holland, Elizabeth A.; Schmid, Helen; Warrier, Sunil; Glasson, William; Höiom, Veronica; Wadt, Karin; Jönsson, Göran; Olsson, Håkan; Ingvar, Christian; Mann, Graham J.; Brown, Kevin M.; Hayward, Nicholas K.; Pritchard, Antonia L.

doi:10.1097/cmr.0000000000000613

Cited by 14 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of other tumor entities have been associated with defects in HRR. The risk of development of cutaneous or uveal malignant melanoma in carriers of BRCA1/2 variants is disputed in the literature 43,44 . Emerging evidence suggests a contribution of HRR‐associated predisposition in a number of other tumors, including medulloblastoma, cholangiocellular carcinoma, colorectal cancer, and sarcoma among others 45‐48 …”

Section: Identification Of Patients With Hrr‐associated Cancer Predismentioning

confidence: 99%

Germline testing for homologous recombination repair genes—opportunities and challenges

Hirsch

Gieldon

Sutter

et al. 2020

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Pathogenic variants in the BRCA1 and BRCA2 genes are well known causes of hereditary breast and ovarian cancer. Other genes involved in the homologous recombination pathway can also be associated with increased probability of cancer development, for example, breast and ovarian cancer, prostate and pancreatic cancer, colorectal cancer, and even childhood tumors like medulloblastoma. Traditionally, patients and families likely to harbor a genetic predisposition have been identified using personal and family history. Several checklists and risk prediction tools have proven to be useful in the clinic. Through the widespread application of next generation sequencing of tumor tissue, a growing number of individuals with genetic cancer predisposition is now identified molecularly, even in the absence of a suggestive family history. Any constitutional variant identified during molecular genetic testing has to be assessed for its relevance, both functionally and in the context of patient phenotype. Variant curation is time consuming, but has been increasingly standardized by introduction of several guidelines to allow reliable and reproducible classification of constitutional variants. Variant classification by expert panels using data mining tools, evidence‐based decision trees and gene specific criteria represents the gold standard. Participation of geneticists in molecular tumor boards facilitates the curation of potential constitutional variants, germline validation and thus directing the patient to appropriate counselling and care pathways. Due to the high relevance of germline variants for treatment and surveillance of the index patient and predictive testing and surveillance of relatives, only pathogenic or likely pathogenic variants must be used for clinical decision‐making.

show abstract

Section: Identification Of Patients With Hrr‐associated Cancer Predismentioning

confidence: 99%

Germline testing for homologous recombination repair genes—opportunities and challenges

Hirsch

Gieldon

Sutter

et al. 2020

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…Literature suggests a possible association between germline BRCA2 pathogenic variants and an elevated risk for melanoma. is possible link has been suggested for both cutaneous and ocular melanoma in BRCA2, but data are conflicting and mainly based on small studies at risk for sampling bias [9,15,21,77]. Overall there seems to be insufficient evidence for a clear correlation between skin and uveal melanoma and germline BRCA pathogenic variants.…”

Section: Belgian Society Of Human Genetics Surveillance and Preventimentioning

confidence: 99%

Cancer Surveillance in Healthy Carriers of Germline Pathogenic Variants in BRCA1/2: A Review of Secondary Prevention Guidelines

Dullens

Putter

Lambertini

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Germline pathogenic alterations in the breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the most prevalent causes of hereditary breast and ovarian cancer. The increasing trend in proportion of cancer patients undergoing genetic testing, followed by predictive testing in families of new index patients, results in a significant increase of healthy germline BRCA1/2 mutation carriers who are at increased risk for breast, ovarian, and other BRCA-related cancers. This review aims to give an overview of available screening guidelines for female and male carriers of pathogenic or likely pathogenic germline BRCA1/2 variants per cancer type, incorporating malignancies that are more or less recently well correlated with BRCA1/2. We selected guidelines from national/international organizations and/or professional associations that were published or updated between January 1, 2015, and February 1, 2020. In total, 12 guidelines were included. This review reveals several significant discordances between the different guidelines. Optimal surveillance strategies depend on accurate age-specific cancer risk estimates, which are not reliably available for all BRCA-related cancers. Up-to-date national or international consensus guidelines are of utmost importance to harmonize counseling and proposed surveillance strategies for BRCA1/2 carriers.

show abstract

“…Until recently, genetic testing involved clinical assessment followed by sequential, single gene Sanger sequencing of suspect genes [ 152 , 153 , 154 , 155 , 156 ]. The advent of NGS brought high throughput germline multigene panel [ 157 , 158 , 159 , 160 , 161 ], whole exome [ 162 , 163 , 164 , 165 , 166 , 167 ] and whole genome assessment [ 168 , 169 , 170 , 171 , 172 ] to clinical cancer genetics. These platforms provide tremendous benefit to cancer genetics patients both in community oncology practices and at academic cancer centers; these advantages include increased diagnostic yield, increased speed of testing, optimized testing workflows, decreased expense and the discovery of new cancer-causing genes [ 173 , 174 , 175 , 176 , 177 ].…”

Section: The Community Oncology/academic Cancer Center Alliance Inmentioning

confidence: 99%

The Community Oncology and Academic Medical Center Alliance in the Age of Precision Medicine: Cancer Genetics and Genomics Considerations

Melas

Subbiah

Saadat

et al. 2020

JCM

View full text Add to dashboard Cite

Recent public policy, governmental regulatory and economic trends have motivated the establishment and deepening of community health and academic medical center alliances. Accordingly, community oncology practices now deliver a significant portion of their oncology care in association with academic cancer centers. In the age of precision medicine, this alliance has acquired critical importance; novel advances in nucleic acid sequencing, the generation and analysis of immense data sets, the changing clinical landscape of hereditary cancer predisposition and ongoing discovery of novel, targeted therapies challenge community-based oncologists to deliver molecularly-informed health care. The active engagement of community oncology practices with academic partners helps with meeting these challenges; community/academic alliances result in improved cancer patient care and provider efficacy. Here, we review the community oncology and academic medical center alliance. We examine how practitioners may leverage academic center precision medicine-based cancer genetics and genomics programs to advance their patients’ needs. We highlight a number of project initiatives at the City of Hope Comprehensive Cancer Center that seek to optimize community oncology and academic cancer center precision medicine interactions.

show abstract

Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma

Cited by 14 publications

References 48 publications

Germline testing for homologous recombination repair genes—opportunities and challenges

Germline testing for homologous recombination repair genes—opportunities and challenges

Cancer Surveillance in Healthy Carriers of Germline Pathogenic Variants in BRCA1/2: A Review of Secondary Prevention Guidelines

The Community Oncology and Academic Medical Center Alliance in the Age of Precision Medicine: Cancer Genetics and Genomics Considerations

Contact Info

Product

Resources

About