Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify et...

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Vydáno v:Investigative ophthalmology & visual science Ročník 65; číslo 4; s. 24
Hlavní autoři: Gleber-Netto, Frederico O., Nagarajan, Priyadharsini, Sagiv, Oded, Pickering, Curtis R., Gross, Neil, Ning, Jing, Yeshi, Melisachew M., Mitku, Yonas, Tetzlaff, Michael T., Esmaeli, Bita
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States The Association for Research in Vision and Ophthalmology 01.04.2024
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ISSN:1552-5783, 0146-0404, 1552-5783
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Abstract Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.
AbstractList Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.
Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies.PurposeConjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies.We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas.MethodsWe compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas.Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs.ResultsSolar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs.Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.ConclusionsOur findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.
Author Ning, Jing
Yeshi, Melisachew M.
Sagiv, Oded
Pickering, Curtis R.
Tetzlaff, Michael T.
Mitku, Yonas
Gross, Neil
Gleber-Netto, Frederico O.
Esmaeli, Bita
Nagarajan, Priyadharsini
Author_xml – sequence: 1
  givenname: Frederico O.
  surname: Gleber-Netto
  fullname: Gleber-Netto, Frederico O.
  organization: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
– sequence: 2
  givenname: Priyadharsini
  surname: Nagarajan
  fullname: Nagarajan, Priyadharsini
  organization: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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  givenname: Oded
  surname: Sagiv
  fullname: Sagiv, Oded
  organization: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States, The Goldschleger Eye Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
– sequence: 4
  givenname: Curtis R.
  surname: Pickering
  fullname: Pickering, Curtis R.
  organization: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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  surname: Gross
  fullname: Gross, Neil
  organization: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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  fullname: Ning, Jing
  organization: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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  givenname: Melisachew M.
  surname: Yeshi
  fullname: Yeshi, Melisachew M.
  organization: Department of Pathology, Mekelle University, Mekelle, Ethiopia
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  givenname: Yonas
  surname: Mitku
  fullname: Mitku, Yonas
  organization: Department of Ophthalmology, Mekelle University, Mekelle, Ethiopia
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  givenname: Michael T.
  surname: Tetzlaff
  fullname: Tetzlaff, Michael T.
  organization: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
– sequence: 10
  givenname: Bita
  surname: Esmaeli
  fullname: Esmaeli, Bita
  organization: Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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Present affiliation: ‡Department of Pathology, University of California - San Francisco, San Francisco, California, United States.
FOGN, PN and OS contributed equally to this work.
Present affiliation: †Department of Surgery-Otolaryngology, Yale School of Medicine, New Haven, Connecticut, United States.
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Snippet Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This...
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StartPage 24
SubjectTerms Anatomy and Pathology/Oncology
Black People
Conjunctiva
Genomics
Humans
Papillomavirus Infections - genetics
Ultraviolet Rays
Title Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden
URI https://www.ncbi.nlm.nih.gov/pubmed/38597722
https://www.proquest.com/docview/3035537615
https://pubmed.ncbi.nlm.nih.gov/PMC11008748
Volume 65
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