PUBLICATIONS NEWS

EVENTS

&

[HetColi] – Cyclin A2/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress. - Published on 07 12 2018
2018 Dec 7, doi:  10.1038/s41467-018-07552-9
Quentin Bayard, Léa Meunier, Camille Peneau, Victor Renault, Jayendra Shinde, Jean-Charles Nault, Iadh Mami, Gabrielle Couchy, Giuliana Amaddeo, Emmanuel Tubacher, Delphine Bacq, Vincent Meyer, Tiziana La Bella, Audrey Debaillon-Vesque, Paulette Bioulac-Sage, Olivier Seror, Jean-Frédéric Blanc, Julien Calderaro, Jean-François Deleuze, Sandrine Imbeaud, Jessica Zucman-Rossi & Eric Letouzé

Abstract

Cyclins A2 and E1 regulate the cell cycle by promoting S phase entry and progression. Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. Cyclin A2 or E1 alterations define a homogenous entity of aggressive HCC, mostly developed in non-cirrhotic patients, characterized by a transcriptional activation of E2F and ATR pathways and a high frequency of RB1 and PTEN inactivation. Cyclin-driven HCC display a unique signature of structural rearrangements with hundreds of tandem duplications and templated insertions frequently activating TERT promoter. These rearrangements, strongly enriched in early-replicated active chromatin regions, are consistent with a break-induced replication mechanism. Pan-cancer analysis reveals a similar signature in BRCA1-mutated breast and ovarian cancers. Together, this analysis reveals a new poor prognosis HCC entity and a rearrangement signature related to replication stress.

Leave a Reply

Your email address will not be published. Required fields are marked *

icon 1

HTE News and Events

icon 2

Last HTE Program
Partners Publications

icon 3

Last International
Publications

This French program is organized by ITMO Cancer, in collaboration with ITMO BCDE (Cell Biology, Development and Evolution) and ITMO Technologies for Health of the National Alliance for Life Sciences and Health (AVIESAN) with the National Cancer Institute (INCA) and Inserm within the framework of the Cancer Plan. Operational management is entrusted to Inserm.
It was launch in order to develop a critical mass of resources and skills in order to conduct interdisciplinary research projects in the field of functional heterogeneity of cellular tumor relations in their ecosystem: the "HTE Program".

Initiation of HTE Program