PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation?
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
20 10 2020
20 10 2020
Historique:
received:
13
05
2020
revised:
14
06
2020
accepted:
15
06
2020
pubmed:
23
6
2020
medline:
31
8
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
Hereditary cancer syndromes represent ~10% of all incident cancers. It is important to identify individuals having these disorders because, unlike patients with sporadic cancer, these patients require specialised life-long care, with implications for their families. Importantly, the identification of alterations in cancer-predisposing genes facilitates gene-informed molecular diagnosis, cancer risk assessment and gene-specific clinical management. Moreover, knowledge about gene function in the inherited cancers offers insights towards biological processes pertinent to the more common sporadic cancers. Conversely, without a known gene, clinical management is less precise, and it is impossible to offer predictive testing of family members. PTEN hamartoma tumour syndrome (PHTS) is an umbrella term encompassing four overgrowth and cancer predisposition disorders associated with germline PTEN mutations. With time, it became evident that only a finite subset of individuals with PHTS-associated phenotypes harbour germline PTEN mutations. Therefore, non-PTEN aetiologies exist in PTEN wildtype patients. Indeed, gene discovery efforts over the last decade elucidated multiple candidate cancer predisposition genes. While a subset of genes (e.g. AKT1, PIK3CA) are biologically plausible as being key effectors within the PTEN signalling cascade, other genes required meticulous functional interrogation to explain their contribution to PHTS-related phenotypes. Collectively, the extensive phenotypic heterogeneity of the clinical syndromes typically united by PTEN is reflected by the genetic heterogeneity revealed through gene discovery. Validating these gene discoveries is critical because, while PTEN wildtype patients can be diagnosed clinically, they do not have the benefit of specific gene-informed risk assessment and subsequent management.
Identifiants
pubmed: 32568377
pii: 5860823
doi: 10.1093/hmg/ddaa127
pmc: PMC7574959
doi:
Substances chimiques
Biomarkers, Tumor
0
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
R150-R157Subventions
Organisme : NCI NIH HHS
ID : P01 CA124570
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS092090
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA111989
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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