Further delineation of the NTHL1 associated syndrome: A report from the French Oncogenetic Consortium.
Adenomatous Polyposis Coli
/ genetics
Adult
Aged
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ genetics
Colorectal Neoplasms
/ genetics
Deoxyribonuclease (Pyrimidine Dimer)
/ genetics
Female
Germ-Line Mutation
Heterozygote
Humans
Male
Middle Aged
Neoplastic Syndromes, Hereditary
/ genetics
Ovarian Neoplasms
/ genetics
Pedigree
Reverse Transcriptase Polymerase Chain Reaction
NTHL1 protein, human
adenomatous polyps
biallelic germline NTHL1 variant
colonic neoplasm
multi-tumor syndrome
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
21
12
2020
received:
04
11
2020
accepted:
10
01
2021
pubmed:
18
1
2021
medline:
1
2
2022
entrez:
17
1
2021
Statut:
ppublish
Résumé
Biallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra-colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the "colorectal cancer or polyposis" series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra-digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra-colonic surveillance has to be defined.
Substances chimiques
Biomarkers, Tumor
0
Deoxyribonuclease (Pyrimidine Dimer)
EC 3.1.25.1
NTHL1 protein, human
EC 3.1.25.1
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
662-672Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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