TY - JOUR
T1 - Integrative transcriptome analyses of the human fallopian tube
T2 - Fimbria and ampulla—site of origin of serous carcinoma of the ovary
AU - Sowamber, Ramlogan
AU - Nelson, Omar
AU - Dodds, Leah
AU - Decastro, Victoria
AU - Paudel, Iru
AU - Milea, Anca
AU - Considine, Michael
AU - Cope, Leslie
AU - Pinto, Andre
AU - Schlumbrecht, Matthew
AU - Slomovitz, Brian
AU - Shaw, Patricia A.
AU - George, Sophia H.L.
N1 - Funding Information:
We thank the UHN Biobank and SCCC Biospecimen Shared Resource (Guillermo Morales and Luis Diaz) for sample acquisition, and University of Miami Confocal Core for digital imaging and image analysis services (Gabriel Gaidosh). We also thank Noor Salman, Zahra Maamir, Nick Chauvin, Gillian Geddie and Wendelle Henry. This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), Foundation for Women’s Cancer, Belinda Sue Fund, Colleen’s Dream Foundation and Sylvester Comprehensive Cancer Center. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA240139. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
Acknowledgments: We thank the UHN Biobank and SCCC Biospecimen Shared Resource (Guillermo Morales and Luis Diaz) for sample acquisition, and University of Miami Confocal Core for digital imaging and image analysis services (Gabriel Gaidosh). We also thank Noor Salman, Zahra Maamir, Nick Chauvin, Gillian Geddie and Wendelle Henry. This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), Foundation for Women’s Cancer, Belinda Sue Fund, Colleen’s Dream Foundation and Sylvester Comprehensive Cancer Center. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA240139. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - Ampulla
KW - Differentially expressed genes (DEGs)
KW - Fallopian tube
KW - Fimbria
KW - Laser capture microdissection
KW - Ovarian cancer
KW - Transcriptomic analysis
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U2 - 10.3390/cancers12051090
DO - 10.3390/cancers12051090
M3 - Article
C2 - 32349388
AN - SCOPUS:85083981207
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 5
M1 - 1090
ER -