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1 April 2022
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Somatic mosaicism, where two or more cell populations have different genotypes, can occur in normal cells as they undergo mutagenesis over an individual's life span. These mosaic variants can arise early in embryogenesis and be present in adult tissues. Mosaicism in cancer susceptibility genes has been observed in individuals with clinical features of hereditary predisposition syndromes, but the contribution of these mosaic variants to the development of apparently sporadic cancers has yet to be defined. Pareja, Ptashkin, Brown, and colleagues analyzed paired tumor/blood sequencing data from over 35,000 unselected patients with cancer and showed that mosaic variants affecting cancer susceptibility genes can occur early in embryogenesis and are likely to contribute to tumorigenesis, thereby increasing the risk for developing cancer. The detection of these variants may ultimately influence clinical decisions as well as preventive measures for patients and their offspring. For more information, see the article by Pareja, Ptashkin, Brown, and colleagues on page 949. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Genomic Landscape and Clinical Utility in Korean Advanced Pan-Cancer Patients from Prospective Clinical Sequencing: K-MASTER Program
Kyong Hwa Park; Jung Yoon Choi; Ah-Reum Lim; Ju Won Kim; Yoon Ji Choi; Soohyeon Lee; Jae Sook Sung; Hee-Joon Chung; Byunghyun Jang; Dayoung Yoon; Sukwon Kim; Jason K. Sa; Yeul Hong Kim
Cancer-Causative Mutations Occurring in Early Embryogenesis
Fresia Pareja; Ryan N. Ptashkin; David N. Brown; Fatemeh Derakhshan; Pier Selenica; Edaise M. da Silva; Andrea M. Gazzo; Arnaud Da Cruz Paula; Kelsey Breen; Ronglai Shen; Antonio Marra; Ahmet Zehir; Ryma Benayed; Michael F. Berger; Ozge Ceyhan-Birsoy; Sowmya Jairam; Margaret Sheehan; Utsav Patel; Yelena Kemel; Jacklyn Casanova-Murphy; Christopher J. Schwartz; Mahsa Vahdatinia; Elizabeth Comen; Laetitia Borsu; Xin Pei; Nadeem Riaz; David H. Abramson; Britta Weigelt; Michael F. Walsh; Anna-Katerina Hadjantonakis; Marc Ladanyi; Kenneth Offit; Zsofia K. Stadler; Mark E. Robson; Jorge S. Reis-Filho; Diana Mandelker
Research Articles
The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals
Jean-Eudes Fahrner; Imran Lahmar; Anne-Gaëlle Goubet; Yacine Haddad; Agathe Carrier; Marine Mazzenga; Damien Drubay; Carolina Alves Costa Silva; Lyon COVID Study Group; Eric de Sousa; Cassandra Thelemaque; Cléa Melenotte; Agathe Dubuisson; Arthur Geraud; Gladys Ferrere; Roxanne Birebent; Camille Bigenwald; Marion Picard; Luigi Cerbone; Joana R. Lérias; Ariane Laparra; Alice Bernard-Tessier; Benoît Kloeckner; Marianne Gazzano; François-Xavier Danlos; Safae Terrisse; Eugenie Pizzato; Caroline Flament; Pierre Ly; Eric Tartour; Nadine Benhamouda; Lydia Meziani; Abdelhakim Ahmed-Belkacem; Makoto Miyara; Guy Gorochov; Fabrice Barlesi; Alexandre Trubert; Benjamin Ungar; Yeriel Estrada; Caroline Pradon; Emmanuelle Gallois; Fanny Pommeret; Emeline Colomba; Pernelle Lavaud; Marc Deloger; Nathalie Droin; Eric Deutsch; Bertrand Gachot; Jean-Philippe Spano; Mansouria Merad; Florian Scotté; Aurélien Marabelle; Frank Griscelli; Jean-Yves Blay; Jean-Charles Soria; Miriam Merad; Fabrice André; Juliette Villemonteix; Mathieu F. Chevalier; Sophie Caillat-Zucman; Florence Fenollar; Emma Guttman-Yassky; Odile Launay; Guido Kroemer; Bernard La Scola; Markus Maeurer; Lisa Derosa; Laurence Zitvogel
In both healthy and cancer-bearing individuals, Th1/Tc1 response of spike protein–specific memory T cells is associated with susceptibility to SARS-CoV-2 infection.
Early Tumor–Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer
Ryul Kim; Minae An; Hyuk Lee; Arnav Mehta; You Jeong Heo; Kyoung-Mee Kim; Song-Yi Lee; Jeonghyeon Moon; Seung Tae Kim; Byung-Hoon Min; Tae Jun Kim; Sun Young Rha; Won Ki Kang; Woong-Yang Park; Samuel J. Klempner; Jeeyun Lee
Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer
Anup Kumar Biswas; Seoyoung Han; Yifan Tai; Wanchao Ma; Courtney Coker; S. Aidan Quinn; Ahmad Rushdi Shakri; Timothy James Zhong; Hanna Scholze; Galina G. Lagos; Angeliki Mela; Katia Manova-Todorova; Elisa de Stanchina; Adolfo A. Ferrando; Cathy Mendelsohn; Peter Canoll; Helena A. Yu; Paul K. Paik; Anjali Saqi; Catherine A. Shu; Mark G. Kris; Joan Massague; Swarnali Acharyya
The S100A9–ALDH1A1–retinoic acid signaling pathway mediates osimertinib resistance and brain relapse in models of EGFR-mutant lung cancer.
Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
Chewei Anderson Chang; Jayu Jen; Shaowen Jiang; Azin Sayad; Arvind Singh Mer; Kevin R. Brown; Allison M.L. Nixon; Avantika Dhabaria; Kwan Ho Tang; David Venet; Christos Sotiriou; Jiehui Deng; Kwok-kin Wong; Sylvia Adams; Peter Meyn; Adriana Heguy; Jane A. Skok; Aristotelis Tsirigos; Beatrix Ueberheide; Jason Moffat; Abhyudai Singh; Benjamin Haibe-Kains; Alireza Khodadadi-Jamayran; Benjamin G. Neel
Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges
Kai Song; Jenna K. Minami; Arthur Huang; Siavash R. Dehkordi; Shirley H. Lomeli; Jens Luebeck; Mark H. Goodman; Gatien Moriceau; Oscar Krijgsman; Prashanthi Dharanipragada; Trevor Ridgley; William P. Crosson; Jesus Salazar; Eli Pazol; Gabriel Karin; Rachana Jayaraman; Nikolas G. Balanis; Salwan Alhani; Kyle Sheu; Johanna ten Hoeve; Amelia Palermo; Stephen E. Motika; T. Niroshi Senaratne; Kim H. Paraiso; Paul J. Hergenrother; P. Nagesh Rao; Asha S. Multani; Daniel S. Peeper; Vineet Bafna; Roger S. Lo; Thomas G. Graeber
A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti–PD-1 Resistance through Effects on the Gut Microbiota
Meriem Messaoudene; Reilly Pidgeon; Corentin Richard; Mayra Ponce; Khoudia Diop; Myriam Benlaifaoui; Alexis Nolin-Lapalme; Florent Cauchois; Julie Malo; Wiam Belkaid; Stephane Isnard; Yves Fradet; Lharbi Dridi; Dominique Velin; Paul Oster; Didier Raoult; François Ghiringhelli; Romain Boidot; Sandy Chevrier; David T. Kysela; Yves V. Brun; Emilia Liana Falcone; Geneviève Pilon; Florian Plaza Oñate; Oscar Gitton-Quent; Emmanuelle Le Chatelier; Sylvere Durand; Guido Kroemer; Arielle Elkrief; André Marette; Bastien Castagner; Bertrand Routy
The polyphenol castalagin acts as a prebiotic and exerts antitumor activity as well as potentiates anti–PD-1 immune efficacy through a beneficial shift in microbiome composition.
Deconvolving Clinically Relevant Cellular Immune Cross-talk from Bulk Gene Expression Using CODEFACS and LIRICS Stratifies Patients with Melanoma to Anti–PD-1 Therapy
Kun Wang; Sushant Patkar; Joo Sang Lee; E. Michael Gertz; Welles Robinson; Fiorella Schischlik; David R. Crawford; Alejandro A. Schäffer; Eytan Ruppin
Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia
Marta Galán-Díez; Florence Borot; Abdullah Mahmood Ali; Junfei Zhao; Eva Gil-Iturbe; Xiaochuan Shan; Na Luo; Yongfeng Liu; Xi-Ping Huang; Brygida Bisikirska; Rossella Labella; Irwin Kurland; Bryan L. Roth; Matthias Quick; Siddhartha Mukherjee; Raul Rabadán; Martin Carroll; Azra Raza; Stavroula Kousteni
Kynurenine secreted by acute myeloid leukemia cells activates the serotonin receptor 1b in osteoblasts to drive leukemia through the acute-phase protein serum amyloid A (SAA), with an increase in both kynurenine and SAA seen in mouse models and patient samples.
Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis
Satoru Yonekura; Safae Terrisse; Carolina Alves Costa Silva; Antoine Lafarge; Valerio Iebba; Gladys Ferrere; Anne-Gaëlle Goubet; Jean-Eudes Fahrner; Imran Lahmar; Kousuke Ueda; Gibrail Mansouri; Eugénie Pizzato; Pierre Ly; Marine Mazzenga; Cassandra Thelemaque; Marine Fidelle; Fanny Jaulin; Jérôme Cartry; Marc Deloger; Marine Aglave; Nathalie Droin; Paule Opolon; Angélique Puget; Fanny Mann; Michel Neunlist; Anne Bessard; Laetitia Aymeric; Tamara Matysiak-Budnik; Jacques Bosq; Paul Hofman; Connie P.M. Duong; Sophie Ugolini; Valentin Quiniou; Sylvie Berrard; Bernhard Ryffel; Oliver Kepp; Guido Kroemer; Bertrand Routy; Leonardo Lordello; Mohamed-Amine Bani; Nicola Segata; Fjodor Yousef Yengej; Hans Clevers; Jean-Yves Scoazec; Edoardo Pasolli; Lisa Derosa; Laurence Zitvogel
Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation
Bappaditya Chandra; Nicole L. Michmerhuizen; Hazheen K. Shirnekhi; Swarnendu Tripathi; Brittany J. Pioso; David W. Baggett; Diana M. Mitrea; Ilaria Iacobucci; Michael R. White; Jingjing Chen; Cheon-Gil Park; Huiyun Wu; Stanley Pounds; Anna Medyukhina; Khaled Khairy; Qingsong Gao; Chunxu Qu; Sherif Abdelhamed; Scott D. Gorman; Simranjot Bawa; Carolyn Maslanka; Swati Kinger; Priyanka Dogra; Mylene C. Ferrolino; Danika Di Giacomo; Cristina Mecucci; Jeffery M. Klco; Charles G. Mullighan; Richard W. Kriwacki
NUP98 fusion oncoproteins promote leukemogenesis by undergoing phase separation in the nuclei of hematopoietic cells to form hundreds of punctate transcriptional condensates that drive aberrant gene expression and induce myeloid transformation.
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