Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients

ABSTRACT We investigated the presence of viral DNA and RNA in cutaneous squamous cell carcinoma (cSCC) tumor and normal tissues from nine individuals with a history of hematopoietic stem cell transplantation (HCT). Microbiome quantification through DNA and RNA sequencing (RNA-seq) revealed the prese...

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Main Authors: Jana K. Dickter, Yuqi Zhao, Vishwas Parekh, Huiyan Ma, Badri G. Modi, Wai-Yee Li, Saro H. Armenian, Xiwei Wu, Farah R. Abdulla
Format: Article
Language:English
Published: American Society for Microbiology 2025-05-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.00053-25
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author Jana K. Dickter
Yuqi Zhao
Vishwas Parekh
Huiyan Ma
Badri G. Modi
Wai-Yee Li
Saro H. Armenian
Xiwei Wu
Farah R. Abdulla
author_facet Jana K. Dickter
Yuqi Zhao
Vishwas Parekh
Huiyan Ma
Badri G. Modi
Wai-Yee Li
Saro H. Armenian
Xiwei Wu
Farah R. Abdulla
author_sort Jana K. Dickter
collection DOAJ
description ABSTRACT We investigated the presence of viral DNA and RNA in cutaneous squamous cell carcinoma (cSCC) tumor and normal tissues from nine individuals with a history of hematopoietic stem cell transplantation (HCT). Microbiome quantification through DNA and RNA sequencing (RNA-seq) revealed the presence of 18 viruses in both tumor and normal tissues. DNA sequencing (DNA-seq) identified Torque teno virus, Saimiriine herpesvirus 1, Merkel cell polyomavirus, Human parvovirus B19, Human gammaherpesvirus-4, Human herpesvirus-6, and others. RNA-seq revealed additional viruses such as Tobamovirus, Pinus nigra virus, Orthohepadnavirus, Human papillomavirus-5, Human herpesvirus-7, Human gammaherpesvirus-4, Gammaretrovirus, and others. Notably, DNA-seq indicated that tumor samples exhibited low levels of Escherichia virus in three out of nine subjects and elevated levels of Human gammaherpesvirus-4 in one subject, while normal samples frequently contained Gammaretrovirus and occasionally Escherichia virus. A comparative analysis using both DNA- and RNA-seq captured three common viruses: Abelson murine leukemia virus, Murine type C retrovirus, and Human gammaherpesvirus-4. These findings were corroborated by an independent data set, supporting the reliability of the viral detection methods utilized. The study provides insights into the viral landscape in post-HCT patients, emphasizing the need for comprehensive viral monitoring in this vulnerable population.IMPORTANCEThis study is important because it explores the potential role of viruses in the development of cSCC in individuals who have undergone allogeneic HCT. cSCC is common in this population, particularly in those with chronic graft-versus-host disease on long-term immunosuppression. By using advanced metagenomic and metatranscriptomic next-generation sequencing, we aimed to identify viral pathogens present in tumor and adjacent normal tissue. The results could lead to targeted preventive or therapeutic interventions for these high-risk people, potentially improving their outcomes and management of cSCC.
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spelling doaj-art-001b0590168e4bbba8943c050be8e4092025-08-20T02:14:44ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-05-0113510.1128/spectrum.00053-25Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipientsJana K. Dickter0Yuqi Zhao1Vishwas Parekh2Huiyan Ma3Badri G. Modi4Wai-Yee Li5Saro H. Armenian6Xiwei Wu7Farah R. Abdulla8Department of Medicine, Division of Infectious Diseases, City of Hope National Medical Center, Duarte, California, USABeckman Research Institute, City of Hope National Medical Center, Duarte, California, USADepartment of Pathology, City of Hope National Medical Center, Duarte, California, USADepartment of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, California, USADepartment of Surgery, Division of Dermatology, City of Hope National Medical Center, Duarte, California, USADepartment of Surgery, Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USADepartment of Population Sciences, Department of Pediatrics, City of Hope National Medical Center, Duarte, California, USABeckman Research Institute, City of Hope National Medical Center, Duarte, California, USADepartment of Surgery, Division of Dermatology, City of Hope National Medical Center, Duarte, California, USAABSTRACT We investigated the presence of viral DNA and RNA in cutaneous squamous cell carcinoma (cSCC) tumor and normal tissues from nine individuals with a history of hematopoietic stem cell transplantation (HCT). Microbiome quantification through DNA and RNA sequencing (RNA-seq) revealed the presence of 18 viruses in both tumor and normal tissues. DNA sequencing (DNA-seq) identified Torque teno virus, Saimiriine herpesvirus 1, Merkel cell polyomavirus, Human parvovirus B19, Human gammaherpesvirus-4, Human herpesvirus-6, and others. RNA-seq revealed additional viruses such as Tobamovirus, Pinus nigra virus, Orthohepadnavirus, Human papillomavirus-5, Human herpesvirus-7, Human gammaherpesvirus-4, Gammaretrovirus, and others. Notably, DNA-seq indicated that tumor samples exhibited low levels of Escherichia virus in three out of nine subjects and elevated levels of Human gammaherpesvirus-4 in one subject, while normal samples frequently contained Gammaretrovirus and occasionally Escherichia virus. A comparative analysis using both DNA- and RNA-seq captured three common viruses: Abelson murine leukemia virus, Murine type C retrovirus, and Human gammaherpesvirus-4. These findings were corroborated by an independent data set, supporting the reliability of the viral detection methods utilized. The study provides insights into the viral landscape in post-HCT patients, emphasizing the need for comprehensive viral monitoring in this vulnerable population.IMPORTANCEThis study is important because it explores the potential role of viruses in the development of cSCC in individuals who have undergone allogeneic HCT. cSCC is common in this population, particularly in those with chronic graft-versus-host disease on long-term immunosuppression. By using advanced metagenomic and metatranscriptomic next-generation sequencing, we aimed to identify viral pathogens present in tumor and adjacent normal tissue. The results could lead to targeted preventive or therapeutic interventions for these high-risk people, potentially improving their outcomes and management of cSCC.https://journals.asm.org/doi/10.1128/spectrum.00053-25cutaneous squamous cell carcinomaviral infectionsallogeneic hematopoietic stem cell transplant survivorswhole-genome sequencingnext-generation sequencingmining metagenome and metatranscriptome
spellingShingle Jana K. Dickter
Yuqi Zhao
Vishwas Parekh
Huiyan Ma
Badri G. Modi
Wai-Yee Li
Saro H. Armenian
Xiwei Wu
Farah R. Abdulla
Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
Microbiology Spectrum
cutaneous squamous cell carcinoma
viral infections
allogeneic hematopoietic stem cell transplant survivors
whole-genome sequencing
next-generation sequencing
mining metagenome and metatranscriptome
title Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
title_full Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
title_fullStr Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
title_full_unstemmed Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
title_short Mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
title_sort mining metagenomes and metatranscriptomes unveils viruses associated with cutaneous squamous cell carcinoma in hematopoietic stem cell transplant recipients
topic cutaneous squamous cell carcinoma
viral infections
allogeneic hematopoietic stem cell transplant survivors
whole-genome sequencing
next-generation sequencing
mining metagenome and metatranscriptome
url https://journals.asm.org/doi/10.1128/spectrum.00053-25
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