Mitchell J Machiela1. 1. Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Abstract
PURPOSE OF REVIEW: Genetic mosaicism is the presence of a somatic mutation in a subset of cells that differs from the inherited germline genome. Detectable genetic mosaicism is attractive as a potential early biomarker for cancer risk because of its established relationship with aging, introduction of potentially deleterious mutations, and clonal selection and expansion of mutated cells. The aim of this review is to survey shared risk factors associated with genetic mosaicism, aging and cancer risk. RECENT FINDINGS: Studies have associated aging, cigarette smoking and several genetic susceptibility loci with increased risk of acquiring genetic mosaicism. Genetic mosaicism has also been associated with numerous outcomes including cancer risk and cancer mortality; however, the level of evidence supporting these associations varies considerably. SUMMARY: Ample evidence exists for shared risk factors for genetic mosaicism and cancer risk as well as abundant support linking genetic mosaicism in leukocytes to hematologic malignancies. The relationship between genetic mosaicism in circulating leukocytes and solid malignancies remains an active area of research.
PURPOSE OF REVIEW: Genetic mosaicism is the presence of a somatic mutation in a subset of cells that differs from the inherited germline genome. Detectable genetic mosaicism is attractive as a potential early biomarker for cancer risk because of its established relationship with aging, introduction of potentially deleterious mutations, and clonal selection and expansion of mutated cells. The aim of this review is to survey shared risk factors associated with genetic mosaicism, aging and cancer risk. RECENT FINDINGS: Studies have associated aging, cigarette smoking and several genetic susceptibility loci with increased risk of acquiring genetic mosaicism. Genetic mosaicism has also been associated with numerous outcomes including cancer risk and cancer mortality; however, the level of evidence supporting these associations varies considerably. SUMMARY: Ample evidence exists for shared risk factors for genetic mosaicism and cancer risk as well as abundant support linking genetic mosaicism in leukocytes to hematologic malignancies. The relationship between genetic mosaicism in circulating leukocytes and solid malignancies remains an active area of research.
Authors: Lars A Forsberg; Chiara Rasi; Hamid R Razzaghian; Geeta Pakalapati; Lindsay Waite; Krista Stanton Thilbeault; Anna Ronowicz; Nathan E Wineinger; Hemant K Tiwari; Dorret Boomsma; Maxwell P Westerman; Jennifer R Harris; Robert Lyle; Magnus Essand; Fredrik Eriksson; Themistocles L Assimes; Carlos Iribarren; Eric Strachan; Terrance P O'Hanlon; Lisa G Rider; Frederick W Miller; Vilmantas Giedraitis; Lars Lannfelt; Martin Ingelsson; Arkadiusz Piotrowski; Nancy L Pedersen; Devin Absher; Jan P Dumanski Journal: Am J Hum Genet Date: 2012-02-02 Impact factor: 11.025
Authors: Mitchell J Machiela; Weiyin Zhou; Neil Caporaso; Michael Dean; Susan M Gapstur; Lynn Goldin; Nathaniel Rothman; Victoria L Stevens; Meredith Yeager; Stephen J Chanock Journal: Blood Adv Date: 2017-02-13
Authors: Jason Y Y Wong; Helene G Margolis; Mitchell Machiela; Weiyin Zhou; Michelle C Odden; Bruce M Psaty; John Robbins; Rena R Jones; Jerome I Rotter; Stephen J Chanock; Nathaniel Rothman; Qing Lan; Jennifer S Lee Journal: Environ Int Date: 2018-04-24 Impact factor: 9.621
Authors: Paul D P Pharoah; Honglin Song; Ed Dicks; Maria P Intermaggio; Patricia Harrington; Caroline Baynes; Kathryn Alsop; Natalia Bogdanova; Mine S Cicek; Julie M Cunningham; Brooke L Fridley; Aleksandra Gentry-Maharaj; Peter Hillemanns; Shashi Lele; Jenny Lester; Valerie McGuire; Kirsten B Moysich; Samantha Poblete; Weiva Sieh; Lara Sucheston-Campbell; Martin Widschwendter; Alice S Whittemore; Thilo Dörk; Usha Menon; Kunle Odunsi; Ellen L Goode; Beth Y Karlan; David D Bowtell; Simon A Gayther; Susan J Ramus Journal: J Natl Cancer Inst Date: 2016-01-27 Impact factor: 13.506
Authors: Cathy C Laurie; Cecelia A Laurie; Kenneth Rice; Kimberly F Doheny; Leila R Zelnick; Caitlin P McHugh; Hua Ling; Kurt N Hetrick; Elizabeth W Pugh; Chris Amos; Qingyi Wei; Li-e Wang; Jeffrey E Lee; Kathleen C Barnes; Nadia N Hansel; Rasika Mathias; Denise Daley; Terri H Beaty; Alan F Scott; Ingo Ruczinski; Rob B Scharpf; Laura J Bierut; Sarah M Hartz; Maria Teresa Landi; Neal D Freedman; Lynn R Goldin; David Ginsburg; Jun Li; Karl C Desch; Sara S Strom; William J Blot; Lisa B Signorello; Sue A Ingles; Stephen J Chanock; Sonja I Berndt; Loic Le Marchand; Brian E Henderson; Kristine R Monroe; John A Heit; Mariza de Andrade; Sebastian M Armasu; Cynthia Regnier; William L Lowe; M Geoffrey Hayes; Mary L Marazita; Eleanor Feingold; Jeffrey C Murray; Mads Melbye; Bjarke Feenstra; Jae H Kang; Janey L Wiggs; Gail P Jarvik; Andrew N McDavid; Venkatraman E Seshan; Daniel B Mirel; Andrew Crenshaw; Nataliya Sharopova; Anastasia Wise; Jess Shen; David R Crosslin; David M Levine; Xiuwen Zheng; Jenna I Udren; Siiri Bennett; Sarah C Nelson; Stephanie M Gogarten; Matthew P Conomos; Patrick Heagerty; Teri Manolio; Louis R Pasquale; Christopher A Haiman; Neil Caporaso; Bruce S Weir Journal: Nat Genet Date: 2012-05-06 Impact factor: 38.330
Authors: Mitchell J Machiela; Weiyin Zhou; Neil Caporaso; Michael Dean; Susan M Gapstur; Lynn Goldin; Victoria L Stevens; Meredith Yeager; Stephen J Chanock Journal: J Hum Genet Date: 2016-01-14 Impact factor: 3.172
Authors: Mitchell J Machiela; Weiyin Zhou; Eric Karlins; Joshua N Sampson; Neal D Freedman; Qi Yang; Belynda Hicks; Casey Dagnall; Christopher Hautman; Kevin B Jacobs; Christian C Abnet; Melinda C Aldrich; Christopher Amos; Laufey T Amundadottir; Alan A Arslan; Laura E Beane-Freeman; Sonja I Berndt; Amanda Black; William J Blot; Cathryn H Bock; Paige M Bracci; Louise A Brinton; H Bas Bueno-de-Mesquita; Laurie Burdett; Julie E Buring; Mary A Butler; Federico Canzian; Tania Carreón; Kari G Chaffee; I-Shou Chang; Nilanjan Chatterjee; Chu Chen; Constance Chen; Kexin Chen; Charles C Chung; Linda S Cook; Marta Crous Bou; Michael Cullen; Faith G Davis; Immaculata De Vivo; Ti Ding; Jennifer Doherty; Eric J Duell; Caroline G Epstein; Jin-Hu Fan; Jonine D Figueroa; Joseph F Fraumeni; Christine M Friedenreich; Charles S Fuchs; Steven Gallinger; Yu-Tang Gao; Susan M Gapstur; Montserrat Garcia-Closas; Mia M Gaudet; J Michael Gaziano; Graham G Giles; Elizabeth M Gillanders; Edward L Giovannucci; Lynn Goldin; Alisa M Goldstein; Christopher A Haiman; Goran Hallmans; Susan E Hankinson; Curtis C Harris; Roger Henriksson; Elizabeth A Holly; Yun-Chul Hong; Robert N Hoover; Chao A Hsiung; Nan Hu; Wei Hu; David J Hunter; Amy Hutchinson; Mazda Jenab; Christoffer Johansen; Kay-Tee Khaw; Hee Nam Kim; Yeul Hong Kim; Young Tae Kim; Alison P Klein; Robert Klein; Woon-Puay Koh; Laurence N Kolonel; Charles Kooperberg; Peter Kraft; Vittorio Krogh; Robert C Kurtz; Andrea LaCroix; Qing Lan; Maria Teresa Landi; Loic Le Marchand; Donghui Li; Xiaolin Liang; Linda M Liao; Dongxin Lin; Jianjun Liu; Jolanta Lissowska; Lingeng Lu; Anthony M Magliocco; Nuria Malats; Keitaro Matsuo; Lorna H McNeill; Robert R McWilliams; Beatrice S Melin; Lisa Mirabello; Lee Moore; Sara H Olson; Irene Orlow; Jae Yong Park; Ana Patiño-Garcia; Beata Peplonska; Ulrike Peters; Gloria M Petersen; Loreall Pooler; Jennifer Prescott; Ludmila Prokunina-Olsson; Mark P Purdue; You-Lin Qiao; Preetha Rajaraman; Francisco X Real; Elio Riboli; Harvey A Risch; Benjamin Rodriguez-Santiago; Avima M Ruder; Sharon A Savage; Fredrick Schumacher; Ann G Schwartz; Kendra L Schwartz; Adeline Seow; Veronica Wendy Setiawan; Gianluca Severi; Hongbing Shen; Xin Sheng; Min-Ho Shin; Xiao-Ou Shu; Debra T Silverman; Margaret R Spitz; Victoria L Stevens; Rachael Stolzenberg-Solomon; Daniel Stram; Ze-Zhong Tang; Philip R Taylor; Lauren R Teras; Geoffrey S Tobias; David Van Den Berg; Kala Visvanathan; Sholom Wacholder; Jiu-Cun Wang; Zhaoming Wang; Nicolas Wentzensen; William Wheeler; Emily White; John K Wiencke; Brian M Wolpin; Maria Pik Wong; Chen Wu; Tangchun Wu; Xifeng Wu; Yi-Long Wu; Jay S Wunder; Lucy Xia; Hannah P Yang; Pan-Chyr Yang; Kai Yu; Krista A Zanetti; Anne Zeleniuch-Jacquotte; Wei Zheng; Baosen Zhou; Regina G Ziegler; Luis A Perez-Jurado; Neil E Caporaso; Nathaniel Rothman; Margaret Tucker; Michael C Dean; Meredith Yeager; Stephen J Chanock Journal: Nat Commun Date: 2016-06-13 Impact factor: 14.919
Authors: Ivan Y Iourov; Svetlana G Vorsanova; Yuri B Yurov; Maria A Zelenova; Oxana S Kurinnaia; Kirill S Vasin; Sergei I Kutsev Journal: Int J Mol Sci Date: 2020-11-06 Impact factor: 5.923