Deletion of a pseudogene within a fragile site triggers the oncogenic expression of the mitotic CCSER1 gene.


Journal

Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869

Informations de publication

Date de publication:
08 2021
Historique:
received: 13 01 2021
revised: 12 06 2021
accepted: 14 06 2021
entrez: 30 6 2021
pubmed: 1 7 2021
medline: 15 12 2021
Statut: epublish

Résumé

The oncogenic role of common fragile sites (CFS), focal and pervasive gaps in the cancer genome arising from replicative stress, remains controversial. Exploiting the TCGA dataset, we found that in most CFS the genes residing within the associated focal deletions are down-regulated, including proteins involved in tumour immune recognition. In a subset of CFS, however, the residing genes are surprisingly overexpressed. Within the most frequent CFS in this group, FRA4F, which is deleted in up to 18% of cancer cases and harbours the CCSER1 gene, we identified a region which includes an intronic, antisense pseudogene, TMSB4XP8. TMSB4XP8 focal ablation or transcriptional silencing elicits the overexpression of

Identifiants

pubmed: 34187875
pii: 4/8/e202101019
doi: 10.26508/lsa.202101019
pmc: PMC8321653
pii:
doi:

Substances chimiques

CCSER1 protein, human 0
Cell Cycle Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States

Informations de copyright

© 2021 Santoliquido et al.

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Auteurs

Benedetta M Santoliquido (BM)

Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.

Michela Frenquelli (M)

Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

Claudia Contadini (C)

Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.

Stefano Bestetti (S)

Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Marco Gaviraghi (M)

Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

Elisa Barbieri (E)

The Wistar Institute, Gene Expression and Regulation Program, Philadelphia, PA, USA.

Anna De Antoni (A)

DNA Metabolism Laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.

Luca Albarello (L)

Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Angelo Amabile (A)

Vita-Salute San Raffaele University, Milan, Italy.
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.

Alessandro Gardini (A)

The Wistar Institute, Gene Expression and Regulation Program, Philadelphia, PA, USA.

Angelo Lombardo (A)

Vita-Salute San Raffaele University, Milan, Italy.
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.

Claudio Doglioni (C)

Vita-Salute San Raffaele University, Milan, Italy.
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Paolo Provero (P)

Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Neurosciences "Rita Levi Montalcini," University of Torino, Turin, Italy.

Silvia Soddu (S)

Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.

Davide Cittaro (D)

Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Giovanni Tonon (G)

Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy tonon.giovanni@hsr.it.
Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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