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Hereditary cancer risk assessment: new perspectives and challenges for the next-gen sequencing era

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Hereditary cancer risk assessment (HCRA) is a dynamic multi-disciplinary process of estimating probabilities of germline pathogenic variants in cancer susceptibility genes and assessing empiric risks of multiple cancers, based on personal and family histories. HCRA includes both diagnostic and predictive ...

Hereditary cancer risk assessment (HCRA) is a dynamic multi-disciplinary process of estimating probabilities of germline pathogenic variants in cancer susceptibility genes and assessing empiric risks of multiple cancers, based on personal and family histories. HCRA includes both diagnostic and predictive genetic testing, either through standard or next-generation sequencing, genetic counseling, and management of susceptible individuals. HCRA provides individuals with the proper information to empower them to make decisions about cancer screening, risk-reducing procedures, and even reproductive options. Next-generation sequencing has been used to identify new variants for many Mendelian diseases and holds promise to uncover the missing heritability of the most common cancers.
Recently, the American College of Medical Genetics and Genomics (ACMG) published a policy statement on recommendations for reporting incidental findings–those not related to the primary indication for testing but with potential medical utility–in clinical exome and genome sequencing.This working group presented a “minimum list” of Mendelian disorders for which any known pathogenic and expected pathogenic secondary variants would be routinely reported to the clinician who ordered clinical sequencing. Remarkably, most of disorders in this list are hereditary cancer syndromes which can be manifested during childhood. As recommended, these variants would be reported independently from patients’ preferences and age, and the ordering physician would be responsible for providing patients and family members with pre-post test counseling and follow up. Surely, this will bring new challenges for the next-gen sequencing era.
Manuscripts are welcome if they include but are not limited to:
1. hereditary/familial cancer
2. germline susceptibility
3. risk assessment
4. genetic counseling
5. germline testing
6. secondary/incidental findings
7. ethical issues
8. missing heritability
9. variants of unknown significance
10. management


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