Journal article

Suggested application of HER2 breast tumor phenotype for germlineTP53variant classification within ACMG/AMP guidelines

Cristina Fortuno, Jessica Mester, Tina Pesaran, Jeffrey N Weitzel, Jill Dolinsky, Amal Yussuf, Kelly McGoldrick, Judy E Garber, Sharon A Savage, Payal P Khincha, D Gareth Evans, Maria Isabel Achatz, Kim E Nichols, Kara N Maxwell, Joshua D Schiffman, Renata Sandoval, Paul A James, Amanda B Spurdle

Human Mutation | WILEY | Published : 2020


Early onset breast cancer is the most common malignancy in women with Li-Fraumeni syndrome, caused by germline TP53 pathogenic variants. It has repeatedly been suggested that breast tumors from TP53 carriers are more likely to be HER2+ than those of noncarriers, but this information has not been incorporated into variant interpretation models for TP53. Breast tumor pathology is already being used quantitatively for assessing pathogenicity of germline variants in other genes, and it has been suggested that this type of evidence can be incorporated into current American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant class..

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Awarded by NIHR Manchester Biomedical Research Centre

Awarded by National Cancer Institute

Awarded by National Health and Medical Research Council

Funding Acknowledgements

Intramural Research Program of the National Institutes of Health; NIHR Manchester Biomedical Research Centre, Grant/Award Number: IS-BRC-1215-20007; National Cancer Institute, Grant/Award Number: 1R01CA242218-01; University of Queensland; National Health and Medical Research Council, Grant/Award Numbers: ID1061779, ID1177524