Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa

Samuel Terkper Ahuno^{1

2}, Anna-Lisa Doebley^{3

4}, Thomas U Ahearn⁵, Joel Yarney⁶, Nicholas Titiloye⁷, Nancy Hamel⁸, Ernest Adjei⁷, Joe-Nat Clegg-Lamptey^{6

9}, Lawrence Edusei⁶, Baffour Awuah⁷, Xiaoyu Song^{10

11}, Verna Vanderpuye⁶, Mustapha Abubakar⁵, Maire Duggan¹², Daniel G Stover^{13

14}, Kofi Nyarko⁹, John M S Bartlett^{15

16

17}, Francis Aitpillah^{7

18}, Daniel Ansong¹⁹, Kevin L Gardner²⁰, Felix Andy Boateng⁷, Anne M Bowcock^{2

11

21

22}, Carlos Caldas²³, William D Foulkes^{8

24

25}, Seth Wiafe²⁶, Beatrice Wiafe-Addai²⁷, Montserrat Garcia-Closas⁵, Alexander Kwarteng^{1

28}, Gavin Ha²⁹, Jonine D Figueroa^{30

31}, Paz Polak^{32

33

34}; Ghana Breast Health Study Team

Collaborators, Affiliations

Collaborators

Affiliations

¹ Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
² Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
³ Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
⁴ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶ Korle Bu Teaching Hospital, Accra, Ghana.
⁷ Komfo Anokye Teaching Hospital, Kumasi, Ghana.
⁸ Research Institute of the McGill University Health Centre, Montréal, QC, Canada.
⁹ University of Ghana, Accra, Ghana.
¹⁰ Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
¹¹ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
¹² Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
¹³ Stefanie Spielman Comprehensive Breast Cancer, The Ohio State University, Columbus, OH, USA.
¹⁴ Division of Medical Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
¹⁵ Ontario Institute for Cancer Research, Toronto, ON, Canada.
¹⁶ Edinburgh Cancer Research Centre, Edinburgh, United Kingdom.
¹⁷ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹⁸ School of Medicine & Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
¹⁹ Department of Child Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
²⁰ Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
²¹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
²² Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
²³ Cancer Research UK Cambridge Centre, Cambridge, UK.
²⁴ Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Montréal, QC, Canada.
²⁵ Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, QC, Canada.
²⁶ School of Public Health, Loma Linda University, Loma Linda, CA, USA.
²⁷ Peace and Love Hospital, Kumasi, Ghana.
²⁸ Kumasi Center for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
²⁹ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. gha@fredhutch.org.
³⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Jonine.figueroa@ed.ac.uk.
³¹ CRUK Edinburgh Centre, University of Edinburgh, Edinburgh, UK. Jonine.figueroa@ed.ac.uk.
³² Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. paz.polak@mssm.edu.
³³ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. paz.polak@mssm.edu.
³⁴ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. paz.polak@mssm.edu.

PMID: 34535742
PMCID: PMC8448727
DOI: 10.1038/s41698-021-00219-7

Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa

Samuel Terkper Ahuno et al. NPJ Precis Oncol. 2021.

. 2021 Sep 17;5(1):83.

doi: 10.1038/s41698-021-00219-7.

Authors

Collaborators

Affiliations

¹ Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
² Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
³ Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
⁴ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶ Korle Bu Teaching Hospital, Accra, Ghana.
⁷ Komfo Anokye Teaching Hospital, Kumasi, Ghana.
⁸ Research Institute of the McGill University Health Centre, Montréal, QC, Canada.
⁹ University of Ghana, Accra, Ghana.
¹⁰ Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
¹¹ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
¹² Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
¹³ Stefanie Spielman Comprehensive Breast Cancer, The Ohio State University, Columbus, OH, USA.
¹⁴ Division of Medical Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
¹⁵ Ontario Institute for Cancer Research, Toronto, ON, Canada.
¹⁶ Edinburgh Cancer Research Centre, Edinburgh, United Kingdom.
¹⁷ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹⁸ School of Medicine & Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
¹⁹ Department of Child Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
²⁰ Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
²¹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
²² Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
²³ Cancer Research UK Cambridge Centre, Cambridge, UK.
²⁴ Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Montréal, QC, Canada.
²⁵ Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, QC, Canada.
²⁶ School of Public Health, Loma Linda University, Loma Linda, CA, USA.
²⁷ Peace and Love Hospital, Kumasi, Ghana.
²⁸ Kumasi Center for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
²⁹ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. gha@fredhutch.org.
³⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Jonine.figueroa@ed.ac.uk.
³¹ CRUK Edinburgh Centre, University of Edinburgh, Edinburgh, UK. Jonine.figueroa@ed.ac.uk.
³² Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. paz.polak@mssm.edu.
³³ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. paz.polak@mssm.edu.
³⁴ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. paz.polak@mssm.edu.

PMID: 34535742
PMCID: PMC8448727
DOI: 10.1038/s41698-021-00219-7

Abstract

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients.

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Conflict of interest statement

G.H.: Patent application (US16/084,890; Broad Institute). J.M.S.B. reports consultancies from Insight Genetics, Inc., BioNTech AG, Biotheranostics, Inc., Pfizer, Rna Diagnostics Inc., oncoXchange/MedcomXchange Communications Inc, Herbert Smith French Solicitors, Oncocyte Corporation, honoraria from NanoString Technologies, Inc, Oncology Education, Biotheranostics, Inc., MedcomXchange Communications Inc, research funding from Thermo Fisher Scientific, Genoptix, Agendia, NanoString Technologies, Inc., Stratifyer GmbH, Biotheranostics, Inc., travel and accommodations expenses from Biotheranostics, Inc., NanoString Technologies, Inc., Breast Cancer Society of Canada, Scientific Advisory Board participation from MedcomXchange Communications Inc. The remaining authors declare no competing interests.

Figures

**Fig. 1. Co-mutation plot showing association between clinical information and genomic characteristics.**
Patients are represented by the columns ordered by decreasing ctDNA fraction. The top two rows show bar plots of tumor fractions estimated with ichorCNA from cfDNA sequenced with 30× WGS-cfDNA (gold bars) and 0.1× WGS-cfDNA (blue bars) (n = 15 patients). The horizontal line across the bar plot shows the limit of detection of ichorCNA for 0.1× (ctDNA fraction = 3%) and a threshold for 30x (ctDNA fraction = 1%) for the detection of ctDNA. Immunohistochemical stains for ER, PR and HER2+, age, and tumor size classification are presented. Copy number gain and loss of selected driver genes in breast cancers are shown in the bottom panel.

**Fig. 2. Genome-wide copy number profiles of 4 patients from cfDNA sequenced at 30× WGS.**
The x-axis represents chromosomes (chr1-22:X) and y-axis shows log2 copy number. Blue represents copy neutral, i.e., chromosomal loci with standard 2 copies (such as chr3, chr4, and chr5 in P07). Deletions of genomic loci (i.e., chr4p in P01 and P08) are shown in green. Gains (3–4 copies) and amplifications (>4 copies) of chromosomal loci (such as chr8p12 containing ZNF703 genes in P01, P07, P08, and P15) are shown in brown and red colors, respectively. P08 has amplification of the chr17 locus containing *ERBB2*. Arrows indicate the gene and estimated copy number (CN) of the predicted segment by ichorCNA. GU Grade Unknown, G2 moderately differentiated, G3 poorly differentiated, WGS whole-genome sequencing, CN copy number, ER estrogen receptor, PR progesterone receptor, HER2 human epidermal growth factor receptor 2, ctDNA circulating-tumor DNA.

See this image and copyright information in PMC

References

1. Figueroa JD, et al. Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: a population-based case-control study. Int J. Cancer. 2020;147:1535–1547. doi: 10.1002/ijc.32929. - DOI - PMC - PubMed
1. Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 10.3322/caac.21660 (2021). - PubMed
1. Adalsteinsson VA, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat. Commun. 2017;8:1324. doi: 10.1038/s41467-017-00965-y. - DOI - PMC - PubMed
1. Liu, M. C. et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Annals Oncol10.1016/j.annonc.2020.02.011 (2020). - PMC - PubMed
1. Peled M, et al. Cell-free DNA concentration in patients with clinical or mammographic suspicion of breast cancer. Sci. Rep. 2020;10:14601. doi: 10.1038/s41598-020-71357-4. - DOI - PMC - PubMed

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Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa

Collaborators

Affiliations

Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources