Menée in vitro et à l'aide d'un modèle murin dont les cellules NK présentent des mutations au niveau du gène codant pour la chimiokine CCL22, cette étude met en évidence un mécanisme par lequel des mutations CCL22 favorisent les maladies lymphoprolifératives en affectant la signalisation des récepteurs couplés aux protéines G ainsi que les interactions entre les cellules NK et les cellules dendritiques

CCL22 mutations drive natural killer cell lymphoproliferative disease by deregulating microenvironmental crosstalk

Baer, Constance ; Kimura, Shunsuke ; Rana, Mitra S. ; Kleist, Andrew B. ; Flerlage, Tim ; Feith, David J. ; Chockley, Peter ; Walter, Wencke ; Meggendorfer, Manja ; Olson, Thomas L. ; Cheon, HeeJin ; Olson, Kristine C. ; Ratan, Aakrosh ; Mueller, Martha-Lena ; Foran, James M. ; Janke, Laura J. ; Qu, Chunxu ; Porter, Shaina N. ; Pruett-Miller, Shondra M. ; Kalathur, Ravi C. ; Haferlach, Claudia ; Kern, Wolfgang ; Paietta, Elisabeth ; Thomas, Paul G. ; Babu, M. Madan ; Loughran, Thomas P. ; Iacobucci, Ilaria ; Haferlach, Torsten ; Mullighan, Charles G.

Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is characterized by clonal expansion of natural killer (NK) cells where the underlying genetic mechanisms are incompletely understood. In the present study, we report somatic mutations in the chemokine gene CCL22 as the hallmark of a distinct subset of CLPD-NK. CCL22 mutations were enriched at highly conserved residues, mutually exclusive of STAT3 mutations and associated with gene expression programs that resembled normal [...]

Cet article présente une approche mathématique permettant de cartographier les interactions entre différents types de cellules à partir de données transcriptomiques à l'échelle d'une seule cellule ou d'une région tissulaire

DIALOGUE maps multicellular programs in tissue from single-cell or spatial transcriptomics data

Jerby-Arnon, Livnat ; Regev, Aviv

Deciphering the functional interactions of cells in tissues remains a major challenge. Here we describe DIALOGUE, a method to systematically uncover multicellular programs (MCPs)—combinations of coordinated cellular programs in different cell types that form higher-order functional units at the tissue level—from either spatial data or single-cell data obtained without spatial information. Tested on spatial datasets from the mouse hypothalamus, cerebellum, visual cortex and neocortex, DIALOGUE [...]

Cet article présente un logiciel en ligne permettant, à l'aide de l'intelligence artificielle et des recommandations de l'"Association for Molecular Pathology", de l'"American Society of Clinical Oncology" et du "College of American Pathologists", de prédire l'oncogénicité de mutations somatiques

CancerVar: An artificial intelligence–empowered platform for clinical interpretation of somatic mutations in cancer

Quan Li ; Zilin Ren ; Kajia Cao ; Marilyn M. Li ; Kai Wang ; Yunyun Zhou

Several knowledgebases are manually curated to support clinical interpretations of thousands of hotspot somatic mutations in cancer. However, discrepancies or even conflicting interpretations are observed among these databases. Furthermore, many previously undocumented mutations may have clinical or functional impacts on cancer but are not systematically interpreted by existing knowledgebases. To address these challenges, we developed CancerVar to facilitate automated and standardized [...]

Menée à l'aide d'un système de traçage de lignées cellulaires introduit dans un modèle murin d'adénocarcinome pulmonaire associé à des mutations oncogènes de KRAS et TRP53, cette étude analyse l'évolution des cellules cancéreuses au cours du développement tumoral

Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution

Yang, Dian ; Jones, Matthew G. ; Naranjo, Santiago ; Rideout, William M., III ; Min, Kyung Hoi ; Ho, Raymond ; Wu, Wei ; Replogle, Joseph M. ; Page, Jennifer L. ; Quinn, Jeffrey J. ; Horns, Felix ; Qiu, Xiaojie ; Chen, Michael Z. ; Freed-Pastor, William A. ; McGinnis, Christopher S. ; Patterson, David M. ; Gartner, Zev J. ; Chow, Eric D. ; Bivona, Trever G. ; Chan, Michelle M. ; Yosef, Nir ; Jacks, Tyler ; Weissman, Jonathan S.

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to [...]

Menée à partir de données génétiques portant sur 185 myxofibrosarcomes, cette étude identifie des anomalies génétiques et analyse leur fréquence

The landscape of genetic aberrations in myxofibrosarcoma

Takeuchi, Yasuhide ; Yoshida, Kenichi ; Halik, Adriane ; Kunitz, Annegret ; Suzuki, Hiromichi ; Kakiuchi, Nobuyuki ; Shiozawa, Yusuke ; Yokoyama, Akira ; Inoue, Yoshikage ; Hirano, Tomonori ; Yoshizato, Tetsuichi ; Aoki, Kosuke ; Fujii, Yoichi ; Nannya, Yasuhito ; Makishima, Hideki ; Pfitzner, Berit Maria ; Bullinger, Lars ; Hirata, Masahiro ; Jinnouchi, Keita ; Shiraishi, Yuichi ; Chiba, Kenichi ; Tanaka, Hiroko ; Miyano, Satoru ; Okamoto, Takeshi ; Haga, Hironori ; Ogawa, Seishi ; Damm, Frederik

Myxofibrosarcoma (MFS) is a rare subtype of sarcoma, whose genetic basis is poorly understood. We analyzed 69 MFS cases using whole-genome (WGS), whole-exome (WES), and/or targeted-sequencing (TS). Newly sequenced genomic data were combined with additional deposited 116 MFS samples. WGS identified a high number of structural variations (SVs) per tumor most frequently affecting the TP53 and RB1 loci, 40% of tumors showed a BRCAness-associated mutation signature, and evidence of chromothripsis [...]