Chemotherapy and the somatic mutation burden of sperm

Shany Picciotto; Camilo Arenas-Gallo; Amos Toren; Ruty Mehrian-Shai; Bryan Daly; Stephen Rhodes; Megan Prunty; Ruolin Liu; Anyull Bohorquez; Marta Grońska-Pęski; Shana Melanaphy; Pamela Callum; Emilie Lassen; Anne-Bine Skytte; Rebecca C. Obeng; Christopher Barbieri; Molly Gallogly; Brenda Cooper; Katherine Daunov; Lydia Beard; Koen Van-Besien; Joshua Halpern; Quintin Pan; Gilad D. Evrony; Viktor A. Adalsteinsson; Jonathan E. Shoag

doi:10.1172/jci.insight.188175

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Picciotto, S. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Arenas-Gallo, C. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Toren, A. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Mehrian-Shai, R. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Daly, B. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Rhodes, S. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Prunty, M. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Liu, R. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Bohorquez, A. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Grońska-Pęski, M. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Melanaphy, S. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Callum, P. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Lassen, E. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Skytte, A. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Obeng, R. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Barbieri, C. in: PubMed | Google Scholar |

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Gallogly, M. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Cooper, B. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Daunov, K. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Beard, L. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Van-Besien, K. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Halpern, J. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Pan, Q. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Evrony, G. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Adalsteinsson, V. in: PubMed | Google Scholar

¹Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, United States of America

²Pediatric Hemato-Oncology, Sheba Medical Center, Ramat Gan, Israel

³Broad Institute of MIT and Harvard, Cambridge, United States of America

⁴Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, United States of America

⁵California Cryobank, Los Angeles, United States of America

⁶Tandem Genetics, Los Angeles, United States of America

⁷Cryos International, Aarhus, Denmark

⁸Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, United States of America

⁹Department of Urology, Weill Cornell Medical College, New York, United States of America

¹⁰Division of Hematology and Cell Therapy, University Hospitals, Seidman Cancer Center, Cleveland, United States of America

¹¹Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Shoag, J. in: PubMed | Google Scholar

Many chemotherapeutic agents impair cancer growth by inducing DNA damage. The impact of these agents on mutagenesis in normal cells, including sperm, is largely unknown. Here, we applied high-fidelity duplex sequencing to 94 samples from 36 individuals exposed to diverse chemotherapies and 32 controls. We found that many of the sperm samples from men exposed to chemotherapy, the mutation burden was elevated as compared to controls and the expected burden based on trio studies, with one subject having >10-fold increase over expected for age. Saliva from this same individual also had a markedly higher mutation burden. We then validated this finding using other tissues, also finding an increased mutation burden in the blood and liver of many subjects exposed to chemotherapy as compared to unexposed controls. Similarly, mice treated with three cycles of cisplatin had an increased mutation burden in sperm but also in the liver, and hematopoietic progenitor cells. These results suggest an association between cancer therapies and mutation burden, with implications for counseling cancer patients considering banking sperm prior to therapy and for cancer survivors considering the tradeoffs of using banked sperm as compared to conceiving naturally.

Chemotherapy and the somatic mutation burden of sperm

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Chemotherapy and the somatic mutation burden of sperm

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