Neuroendocrine Neoplasms Associated with Germline Pathogenic Variants in the Homologous Recombination Pathway.
Endocr Pathol
; 30(3): 237-245, 2019 Sep.
Article
in En
| MEDLINE
| ID: mdl-30772928
ABSTRACT
Neuroendocrine neoplasms (NENs) have been primarily associated with germline pathogenic variants in genes involved in chromatin remodeling (MEN1), cell cycle control (CDKN1B), PI3K/mTOR signaling (TSC1/2, PTEN) as well as pseudohypoxia (VHL, SDHx). Recent work has implicated various genes involved in DNA repair pathways in the pathophysiology of a subset of pancreatic neuroendocrine neoplasms, including BRCA2, via the homologous recombination pathway (HRD). To date, germline variants in other HRD pathway genes have not been described to contribute to NEN. PALB2, RAD51C, and BARD1 are additional tumor suppressor genes which also mediate repair of double stranded DNA breaks through the HRD pathway and are implicated in hereditary breast (PALB2; BARD1) and ovarian (RAD51C) cancer. Here we report three cases of NEN associated with germline pathogenic variants in PALB2 (pancreatic NEN), RAD51C (thymic NEN), and BARD1 (pancreaticoduodenal NEN) respectively, further linking the DNA repair pathway to NENs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neuroendocrine Tumors
/
Germ-Line Mutation
/
Homologous Recombination
Type of study:
Diagnostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Endocr Pathol
Journal subject:
ENDOCRINOLOGIA
/
PATOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Canada