A partir de données extraites de 7 930 échantillons tumoraux prélevés sur des patients atteints d'un cancer (20 types différents), cette étude analyse les mutations somatiques observées dans les gènes du complexe majeur d'histocompatibilité de classe I

Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes

Shukla, Sachet A. ; Rooney, Michael S. ; Rajasagi, Mohini ; Tiao, Grace ; Dixon, Philip M. ; Lawrence, Michael S. ; Stevens, Jonathan ; Lane, William J. ; Dellagatta, Jamie L. ; Steelman, Scott ; Sougnez, Carrie ; Cibulskis, Kristian ; Kiezun, Adam ; Hacohen, Nir ; Brusic, Vladimir ; Wu, Catherine J. ; Getz, Gad

Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor [...]

A partir d'une revue de la littérature portant sur 263 régions chromosomiques associées à un risque de cancer, cette étude suggère que, par rapport à l'ensemble du génome, les mutations somatiques observées ne sont pas plus fréquentes dans ces régions

Limited evidence that cancer susceptibility regions are preferential targets for somatic mutation

Machiela, Mitchell ; Ho, Brian ; Fisher, Victoria ; Hua, Xing ; Chanock, Stephen

BACKGROUND:Genome wide-association studies have successfully identified several hundred independent loci harboring common cancer susceptibility alleles that are distinct from the more than 110 cancer predisposition genes. The latter are generally characterized by disruptive mutations in coding genes that have been established as 'drivers' of cancer in large somatic sequencing studies. We set out to determine whether, similarly, common cancer susceptibility loci map to genes that have altered [...]

Menée sur 4 853 échantillons tumoraux prélevés sur des patients atteints d'une tumeur solide, cette étude analyse les anomalies du gène FGFR par type d'anomalie (amplification, mutation, réarrangement)

The FGFR Landscape in Cancer : Analysis of 4853 Tumors by Next Generation Sequencing

Helsten, Teresa ; Elkin, Sheryl ; Arthur, Elisa ; Tomson, Brett N. ; Carter, Jennifer ; Kurzrock, Razelle

Purpose: Molecular profiling may have prognostic and predictive value, and is increasingly used in the clinical setting. There are more than a dozen fibroblast growth factor receptor (FGFR) inhibitors in development. Optimal therapeutic application of FGFR inhibitors requires knowledge of the rates and types of FGFR aberrations in a variety of cancer types. Experimental Design: We analyzed frequencies of FGFR aberrations in 4853 solid tumors that were, on physician request, tested in a Clinical [...]

A partir d'échantillons tumoraux prélevés sur 69 patients masculins atteints d'un cancer du sein, cette étude identifie la présence fréquente de copies de gènes sur certaines régions chromosomiques permettant de définir un profil évocateur du sous-type BRCA2 des cancers du sein chez les femmes

Copy number profiling by array comparative genomic hybridization identifies frequently occurring BRCA2-like male breast cancer

Biesma, Hedde D. ; Schouten, Philip C. ; Lacle, Miangela M. ; Sanders, Joyce ; Brugman, Wim ; Kerkhoven, Ron ; Mandjes, Ingrid ; van der Groep, Petra ; van Diest, Paul J. ; Linn, Sabine C.

Genomic aberrations can be used to subtype breast cancer. In this study, we investigated DNA copy number (CN) profiles of 69 cases of male breast cancer (MBC) by array comparative genomic hybridization (aCGH) to detect recurrent gains and losses in comparison with female breast cancers (FBC). Further, we classified these profiles as BRCA1-like, BRCA2-like or non-BRCA-like profiles using previous classifiers derived from FBC, and correlated these profiles with pathological characteristics. We [...]

Menée à l'aide de modèles murins de leucémie myéloïde aiguë, cette étude met en évidence des mécanismes par lesquels une réduction, même de faible ampleur, de l'expression du facteur de transcription hématopoïétique PU.1 favorise le développement de la maladie

Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia

Will, Britta ; Vogler, Thomas O. ; Narayanagari, Swathi ; Bartholdy, Boris ; Todorova, Tihomira I. ; da Silva Ferreira, Mariana ; Chen, Jiahao ; Yu, Yiting ; Mayer, Jillian ; Barreyro, Laura ; Carvajal, Luis ; Neriah, Daniela Ben ; Roth, Michael ; van Oers, Johanna ; Schaetzlein, Sonja ; McMahon, Christine ; Edelmann, Winfried ; Verma, Amit ; Steidl, Ulrich

Modest transcriptional changes caused by genetic or epigenetic mechanisms are frequent in human cancer. Although loss or near-complete loss of the hematopoietic transcription factor PU.1 induces acute myeloid leukemia (AML) in mice, a similar degree of PU.1 impairment is exceedingly rare in human AML; yet, moderate PU.1 inhibition is common in AML patients. We assessed functional consequences of modest reductions in PU.1 expression on leukemia development in mice harboring DNA lesions [...]

Cet article passe en revue les travaux récents sur le rôle joué par les cellules tumorales dormantes dans l'évolution d'une tumeur et la résistance thérapeutique

Mechanisms of Cancer Cell Dormancy—Another Hallmark of Cancer?

Yeh, Albert C. ; Ramaswamy, Sridhar

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, [...]