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Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancero...

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Autores principales: Sowamber, Ramlogan, Nelson, Omar, Dodds, Leah, DeCastro, Victoria, Paudel, Iru, Milea, Anca, Considine, Michael, Cope, Leslie, Pinto, Andre, Schlumbrecht, Matthew, Slomovitz, Brian, Shaw, Patricia A., George, Sophia H. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281286/
https://www.ncbi.nlm.nih.gov/pubmed/32349388
http://dx.doi.org/10.3390/cancers12051090
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author Sowamber, Ramlogan
Nelson, Omar
Dodds, Leah
DeCastro, Victoria
Paudel, Iru
Milea, Anca
Considine, Michael
Cope, Leslie
Pinto, Andre
Schlumbrecht, Matthew
Slomovitz, Brian
Shaw, Patricia A.
George, Sophia H. L.
author_facet Sowamber, Ramlogan
Nelson, Omar
Dodds, Leah
DeCastro, Victoria
Paudel, Iru
Milea, Anca
Considine, Michael
Cope, Leslie
Pinto, Andre
Schlumbrecht, Matthew
Slomovitz, Brian
Shaw, Patricia A.
George, Sophia H. L.
author_sort Sowamber, Ramlogan
collection PubMed
description Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.
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spelling pubmed-72812862020-06-19 Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary Sowamber, Ramlogan Nelson, Omar Dodds, Leah DeCastro, Victoria Paudel, Iru Milea, Anca Considine, Michael Cope, Leslie Pinto, Andre Schlumbrecht, Matthew Slomovitz, Brian Shaw, Patricia A. George, Sophia H. L. Cancers (Basel) Article Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer. MDPI 2020-04-27 /pmc/articles/PMC7281286/ /pubmed/32349388 http://dx.doi.org/10.3390/cancers12051090 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sowamber, Ramlogan
Nelson, Omar
Dodds, Leah
DeCastro, Victoria
Paudel, Iru
Milea, Anca
Considine, Michael
Cope, Leslie
Pinto, Andre
Schlumbrecht, Matthew
Slomovitz, Brian
Shaw, Patricia A.
George, Sophia H. L.
Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary
title Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary
title_full Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary
title_fullStr Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary
title_full_unstemmed Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary
title_short Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary
title_sort integrative transcriptome analyses of the human fallopian tube: fimbria and ampulla—site of origin of serous carcinoma of the ovary
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281286/
https://www.ncbi.nlm.nih.gov/pubmed/32349388
http://dx.doi.org/10.3390/cancers12051090
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