Publications de l`équipe

Publications de l’équipe
Génomique et biologie des cancers du sein héréditaires
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Année de publication : 2012
Tatiana Popova, Elodie Manié, Guillaume Rieunier, Virginie Caux-Moncoutier, Carole Tirapo,
Thierry Dubois, Olivier Delattre, Brigitte Sigal-Zafrani, Marc Bollet, Michel Longy, Claude
Houdayer, Xavier Sastre-Garau, Anne Vincent-Salomon, Dominique Stoppa-Lyonnet, Marc-Henri
Stern (2012 Aug 29)
Ploidy and large-scale genomic instability consistently identify basal-like breast
carcinomas with BRCA1/2 inactivation.
Cancer research : 5454-62 : DOI : 10.1158/0008-5472.CAN-12-1470
Résumé
BRCA1 inactivation is a frequent event in basal-like breast carcinomas (BLC). However,
BRCA1 can be inactivated by multiple mechanisms and determining its status is not a trivial
issue. As an alternate approach, we profiled 65 BLC cases using single-nucleotide
polymorphism arrays to define a signature of BRCA1-associated genomic instability. Large-
scale state transitions (LST), defined as chromosomal break between adjacent regions of at
least 10 Mb, were found to be a robust indicator of BRCA1 status in this setting. Two major
ploidy-specific cutoffs in LST distributions were sufficient to distinguish highly rearranged
BLCs with 85% of proven BRCA1-inactivated cases from less rearranged BLCs devoid of
proven BRCA1-inactivated cases. The genomic signature we defined was validated in a
second independent series of 55 primary BLC cases and 17 BLC-derived tumor cell lines.
High numbers of LSTs resembling BRCA1-inactivated BLC were observed in 4 primary BLC
cases and 2 BLC cell lines that harbored BRCA2 mutations. Overall, the genomic signature
we defined predicted BRCA1/2 inactivation in BLCs with 100% sensitivity and 90% specificity
(97% accuracy). This assay may ease the challenge of selecting patients for genetic testing
or recruitment to clinical trials of novel emerging therapies that target DNA repair
deficiencies in cancer.
Jordan Madic, Sophie Piperno-Neumann, Vincent Servois, Aurore Rampanou, Maud Milder,
Bénédicte Trouiller, David Gentien, Stéphanie Saada, Franck Assayag, Aurélie Thuleau, Fariba
Nemati, Didier Decaudin, François-Clément Bidard, Laurence Desjardins, Pascale Mariani, Olivier
Lantz, Marc-Henri Stern (2012 May 29)
Pyrophosphorolysis-activated polymerization detects circulating tumor DNA in
metastatic uveal melanoma.
Clinical cancer research : an official journal of the American Association for Cancer Research :
3934-41 : DOI : 10.1158/1078-0432.CCR-12-0309
Résumé
To develop a molecular tool to detect circulating tumor-derived DNA (ctDNA) in the plasma
from patients with uveal melanoma as a marker of tumor burden and monitor treatment
efficacy.

Publications de l’équipe
Génomique et biologie des cancers du sein héréditaires
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2
Année de publication : 2011
Virginie Jacquemin, Guillaume Rieunier, Sandrine Jacob, Dorine Bellanger, Catherine Dubois
d'Enghien, Anthony Laugé, Dominique Stoppa-Lyonnet, Marc-Henri Stern (2011 Nov 11)
Underexpression and abnormal localization of ATM products in ataxia
telangiectasia patients bearing ATM missense mutations.
European journal of human genetics : EJHG : 305-12 : DOI : 10.1038/ejhg.2011.196
Résumé
Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by
progressive cerebellar ataxia, oculocutaneous telangiectasia, immune defects and
predisposition to malignancies. A-T is caused by biallelic inactivation of the ATM gene, in
most cases by frameshift or nonsense mutations. More rarely, ATM missense mutations with
unknown consequences on ATM function are found, making definitive diagnosis more
challenging. In this study, a series of 15 missense mutations, including 11 not previously
reported, were identified in 16 patients with clinical diagnosis of A-T belonging to 14 families
and 1 patient with atypical clinical features. ATM function was evaluated in patient
lymphoblastoid cell lines by measuring H2AX and KAP1 phosphorylation in response to
ionizing radiation, confirming the A-T diagnosis for 16 cases. In accordance with previous
studies, we showed that missense mutations associated with A-T often lead to ATM protein
underexpression (15 out of 16 cases). In addition, we demonstrated that most missense
mutations lead to an abnormal cytoplasmic localization of ATM, correlated with its decreased
expression. This new finding highlights ATM mislocalization as a new mechanism of ATM
dysfunction, which may lead to therapeutic strategies for missense mutation associated A-T.
Année de publication : 2010
Julien Bouley, Cédric Pionneau, Justine Varinot, Denis Biard, Catherine Genestie, Martine Antoine,
Florence Coulet, Marc-Henri Stern, Dominique Stoppa-Lyonnet, Florent Soubrier (2010 Dec 8)
Proteomic analysis of BRCA1-depleted cell line reveals a putative role for
replication protein A2 up-regulation in BRCA1 breast tumor development.
Proteomics. Clinical applications : 489-98 : DOI : 10.1002/prca.200900107
Résumé
Germline mutations in BRCA1 result in a strong predisposition to breast cancer, with frequent
loss of heterozygosity of the remaining wild-type allele. The development of BRCA1 tumors is
likely to depend on additional genetic alterations and gene expression changes which follow
growth and DNA repair defects associated with BRCA1 deficiency. The identification of these
modifications offers an opportunity to find surrogate markers of BRCA1 tumors. Here, we
sought to identify differentially expressed proteins related to BRCA1 depletion.

Publications de l’équipe
Génomique et biologie des cancers du sein héréditaires
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3