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Advancing Precision Oncology in Hereditary Paraganglioma-Pheochromocytoma Syndromes: Integrated Interpretation and Data Sharing of the Germline and Tumor Genomes.
Rana, Huma Q; Koeller, Diane R; Walker, McKenzie; Unal, Busra; Levine, Alison Schwartz; Chittenden, Anu; Isidro, Raymond A; Hayes, Connor P; Manam, Monica D; Buehler, Ryan M; Manning, Danielle K; Barletta, Justine A; Hornick, Jason L; Garber, Judy E; Ghazani, Arezou A.
Afiliação
  • Rana HQ; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Koeller DR; Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Walker M; Harvard Medical School, Boston, MA 02115, USA.
  • Unal B; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Levine AS; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Chittenden A; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Isidro RA; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Hayes CP; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Manam MD; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Buehler RM; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Manning DK; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Barletta JA; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Hornick JL; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Garber JE; Harvard Medical School, Boston, MA 02115, USA.
  • Ghazani AA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Int2grate Oncology Consortium; Harvard Medical School, Boston, MA 02115, USA.
Cancers (Basel) ; 16(5)2024 02 26.
Article em En | MEDLINE | ID: mdl-38473309
ABSTRACT
Standard methods of variant assessment in hereditary cancer susceptibility genes are limited by the lack of availability of key supporting evidence. In cancer, information derived from tumors can serve as a useful source in delineating the tumor behavior and the role of germline variants in tumor progression. We have previously demonstrated the value of integrating tumor and germline findings to comprehensively assess germline variants in hereditary cancer syndromes. Building on this work, herein, we present the development and application of the INT2GRATE|HPPGL platform. INT2GRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) is a multi-institution oncology consortium that aims to advance the integrated application of constitutional and tumor data and share the integrated variant information in publicly accessible repositories. The INT2GRATE|HPPGL platform enables automated parsing and integrated assessment of germline, tumor, and genetic findings in hereditary paraganglioma-pheochromocytoma syndromes (HPPGLs). Using INT2GRATE|HPPGL, we analyzed 8600 variants in succinate dehydrogenase (SDHx) genes and their associated clinical evidence. The integrated evidence includes germline variants in SDHx genes; clinical genetics evidence personal and family history of HPPGL-related tumors; tumor-derived evidence somatic inactivation of SDHx alleles, KIT and PDGFRA status in gastrointestinal stromal tumors (GISTs), multifocal or extra-adrenal tumors, and metastasis status; and immunohistochemistry staining status for SDHA and SDHB genes. After processing, 8600 variants were submitted programmatically from the INT2GRATE|HPPGL platform to ClinVar via a custom-made INT2GRATE|HPPGL variant submission schema and an application programming interface (API). This novel integrated variant assessment and data sharing in hereditary cancers aims to improve the clinical assessment of genomic variants and advance precision oncology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos