Clinical Implications of Pathogenic Germline Variants in Small Intestine Neuroendocrine Tumors (SI-NETs).
JCO Precis Oncol
; 5: 808-816, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34994613
ABSTRACT
PURPOSE:
An inherited basis for presumed sporadic neuroendocrine tumor (NET) has been suggested by evidence of familial clustering of NET and a higher incidence of second malignancies in patients and families with NET. To further investigate a potential heritable basis for sporadic neuroendocrine tumors, we performed multigene platform germline analysis to determine the frequency of hereditary susceptibility gene variants in a cohort of patients with sporadic small intestine NET (SI-NET).METHODS:
We performed a multigene platform germline analysis with Invitae's 83-gene, next-generation sequencing panel using DNA from 88 individuals with SI-NET from a clinically annotated database of patients with NET evaluated at Dana-Farber Cancer Institute (DFCI) who are considered high risk for inherited variants. Additionally, we evaluated the prevalence of pathogenic variants in an unselected cohort of patients with SI-NET who underwent testing with Invitae.RESULTS:
Of the 88 patients in the DFCI cohort, a pathogenic germline variant was identified in eight (9%) patients. In an independent cohort of 120 patients with SI-NET, a pathogenic germline variant was identified in 13 (11%) patients. Pathogenic variants were identified in more than one patient in the following genes ATM, RAD51C, MUTYH, and BLM. Somatic testing of tumors from the DFCI cohort was suboptimal because of insufficient coverage of all targeted exons, and therefore, analysis was limited.CONCLUSION:
We demonstrate a 9%-11% incidence of pathogenic germline variants in genes associated with inherited susceptibility for malignancy not previously described in association with SI-NET. The association of these germline variants with neuroendocrine carcinogenesis and risk is uncertain but warrants further characterization.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tumores Neuroendócrinos
/
Neoplasias Intestinais
/
Intestino Delgado
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article