Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers

Evelyn Jiagge; Dexter X. Jin; Justin Y. Newberg; Tomin Perea-Chamblee; Kelly R. Pekala; Christopher Fong; Michele Waters; David Ma; Yvonne Dei-Adomakoh; Gilles Erb; Kanika S. Arora; Sophia L. Maund; Njoki Njiraini; Atara Ntekim; Susie Kim; Xuechun Bai; Marlene Thomas; Ronwyn van Eeden; Priti Hegde; Justin Jee; Debyani Chakravarty; Nikolaus Schultz; Michael F. Berger; Garrett M. Frampton; Ethan S. Sokol; Jian Carrot-Zhang

doi:10.1016/j.ccell.2023.10.003

Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers

Evelyn Jiagge, Dexter X. Jin, Justin Y. Newberg, Tomin Perea-Chamblee, Kelly R. Pekala, Christopher Fong, Michele Waters, David Ma, Yvonne Dei-Adomakoh, Gilles Erb, Kanika S. Arora, Sophia L. Maund, Njoki Njiraini, Atara Ntekim, Susie Kim, Xuechun Bai, Marlene Thomas, Ronwyn van Eeden, Priti Hegde, Justin JeeDebyani Chakravarty, Nikolaus Schultz, Michael F. Berger, Garrett M. Frampton, Ethan S. Sokol, Jian Carrot-Zhang

Department of Haematology

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

8 Citations (Scopus)

Abstract

Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.

Original language	English
Pages (from-to)	1963-1971.e3
Journal	Cancer Cell
Volume	41
Issue number	11
DOIs	https://doi.org/10.1016/j.ccell.2023.10.003
Publication status	Published - 13 Nov 2023

Keywords

African ancestry
driver alteration
next-generation sequencing
precision oncology
real-world data

UN SDGs

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

Access to Document

10.1016/j.ccell.2023.10.003

Cite this

Jiagge, E., Jin, D. X., Newberg, J. Y., Perea-Chamblee, T., Pekala, K. R., Fong, C., Waters, M., Ma, D., Dei-Adomakoh, Y., Erb, G., Arora, K. S., Maund, S. L., Njiraini, N., Ntekim, A., Kim, S., Bai, X., Thomas, M., van Eeden, R., Hegde, P., ... Carrot-Zhang, J. (2023). Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers. Cancer Cell, 41(11), 1963-1971.e3. https://doi.org/10.1016/j.ccell.2023.10.003

@article{6eef41923b664409abda4bc8aeacaedb,

title = "Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers",

abstract = "Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.",

keywords = "African ancestry, driver alteration, next-generation sequencing, precision oncology, real-world data",

author = "Evelyn Jiagge and Jin, {Dexter X.} and Newberg, {Justin Y.} and Tomin Perea-Chamblee and Pekala, {Kelly R.} and Christopher Fong and Michele Waters and David Ma and Yvonne Dei-Adomakoh and Gilles Erb and Arora, {Kanika S.} and Maund, {Sophia L.} and Njoki Njiraini and Atara Ntekim and Susie Kim and Xuechun Bai and Marlene Thomas and {van Eeden}, Ronwyn and Priti Hegde and Justin Jee and Debyani Chakravarty and Nikolaus Schultz and Berger, {Michael F.} and Frampton, {Garrett M.} and Sokol, {Ethan S.} and Jian Carrot-Zhang",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = nov,

day = "13",

doi = "10.1016/j.ccell.2023.10.003",

language = "English",

volume = "41",

pages = "1963--1971.e3",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "11",

}

Jiagge, E, Jin, DX, Newberg, JY, Perea-Chamblee, T, Pekala, KR, Fong, C, Waters, M, Ma, D, Dei-Adomakoh, Y, Erb, G, Arora, KS, Maund, SL, Njiraini, N, Ntekim, A, Kim, S, Bai, X, Thomas, M, van Eeden, R, Hegde, P, Jee, J, Chakravarty, D, Schultz, N, Berger, MF, Frampton, GM, Sokol, ES & Carrot-Zhang, J 2023, 'Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers', Cancer Cell, vol. 41, no. 11, pp. 1963-1971.e3. https://doi.org/10.1016/j.ccell.2023.10.003

TY - JOUR

T1 - Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers

AU - Jiagge, Evelyn

AU - Jin, Dexter X.

AU - Newberg, Justin Y.

AU - Perea-Chamblee, Tomin

AU - Pekala, Kelly R.

AU - Fong, Christopher

AU - Waters, Michele

AU - Ma, David

AU - Dei-Adomakoh, Yvonne

AU - Erb, Gilles

AU - Arora, Kanika S.

AU - Maund, Sophia L.

AU - Njiraini, Njoki

AU - Ntekim, Atara

AU - Kim, Susie

AU - Bai, Xuechun

AU - Thomas, Marlene

AU - van Eeden, Ronwyn

AU - Hegde, Priti

AU - Jee, Justin

AU - Chakravarty, Debyani

AU - Schultz, Nikolaus

AU - Berger, Michael F.

AU - Frampton, Garrett M.

AU - Sokol, Ethan S.

AU - Carrot-Zhang, Jian

PY - 2023/11/13

Y1 - 2023/11/13

N2 - Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.

AB - Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.

KW - African ancestry

KW - driver alteration

KW - next-generation sequencing

KW - precision oncology

KW - real-world data

UR - http://www.scopus.com/inward/record.url?scp=85176094145&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2023.10.003

DO - 10.1016/j.ccell.2023.10.003

M3 - Article

C2 - 37890492

AN - SCOPUS:85176094145

SN - 1535-6108

VL - 41

SP - 1963-1971.e3

JO - Cancer Cell

JF - Cancer Cell

IS - 11

ER -

Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this