Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer

Y. A. Jakubek; K. Chang; S. Sivakumar; Y. Yu; M. R. Giordano; J. Fowler; C. D. Huff; H. Kadara; E. Vilar; P. Scheet

doi:10.1038/s41587-019-0297-6

Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer

Y. A. Jakubek, K. Chang, S. Sivakumar, Y. Yu, M. R. Giordano, J. Fowler, C. D. Huff, H. Kadara, E. Vilar, P. Scheet

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.

Original language	English
Pages (from-to)	90-96
Number of pages	7
Journal	Nature Biotechnology
Volume	38
Issue number	1
DOIs	https://doi.org/10.1038/s41587-019-0297-6
State	Published - Jan 1 2020

Bibliographical note

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Funding

We thank D. Swartzlander for help with the graphics and reviewers for their helpful comments. We acknowledge the High Performance Research Computing Center at the University of Texas, MD Anderson Cancer Center. This work was supported by National Institutes of Health grants R25CA057730 (to Y.A.J.), R01HG005855 (to P.S.), R01HG005859 (to P.S.), R01CA181244 (to P.S. and C.D.H.) and P30CA016672 (to MD Anderson) and by the following awards from the Cancer Prevention Research Institute of Texas: RP150079 (to H.K.) and RP160668 (to P.S.).

Funders	Funder number
National Institutes of Health (NIH)	R25CA057730, P30CA016672, R01CA181244, R01HG005859
National Institutes of Health (NIH)
National Human Genome Research Institute	R01HG005855
National Human Genome Research Institute
Cancer Prevention and Research Institute of Texas	RP160668, RP150079
Cancer Prevention and Research Institute of Texas

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41587-019-0297-6

Cite this

@article{0b17d57ca5ef4b6bb52f63209f491a8f,

title = "Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer",

abstract = "Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.",

author = "Jakubek, \{Y. A.\} and K. Chang and S. Sivakumar and Y. Yu and Giordano, \{M. R.\} and J. Fowler and Huff, \{C. D.\} and H. Kadara and E. Vilar and P. Scheet",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = jan,

day = "1",

doi = "10.1038/s41587-019-0297-6",

language = "English",

volume = "38",

pages = "90--96",

number = "1",

}

TY - JOUR

T1 - Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer

AU - Jakubek, Y. A.

AU - Chang, K.

AU - Sivakumar, S.

AU - Yu, Y.

AU - Giordano, M. R.

AU - Fowler, J.

AU - Huff, C. D.

AU - Kadara, H.

AU - Vilar, E.

AU - Scheet, P.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.

AB - Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.

UR - https://www.scopus.com/pages/publications/85074766074

UR - https://www.scopus.com/inward/citedby.url?scp=85074766074&partnerID=8YFLogxK

U2 - 10.1038/s41587-019-0297-6

DO - 10.1038/s41587-019-0297-6

M3 - Article

C2 - 31685958

AN - SCOPUS:85074766074

SN - 1087-0156

VL - 38

SP - 90

EP - 96

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 1

ER -

Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this