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Using Genomic Variation to Distinguish Ovarian High-Grade Serous Carcinoma from Benign Fallopian Tubes
Journal article   Open access   Peer reviewed

Using Genomic Variation to Distinguish Ovarian High-Grade Serous Carcinoma from Benign Fallopian Tubes

Jesus Gonzalez-Bosquet, Nicholas Cardillo, Henry Reyes, Brian Smith, Kimberly Leslie, David Bender, Michael Goodheart and Eric Devor
International journal of molecular sciences, Vol.23(23), p.14814
12/01/2022
DOI: 10.3390/ijms232314814
PMCID: PMC9738935
PMID: 36499142
url
https://doi.org/10.3390/ijms232314814View
Published (Version of record) Open Access

Abstract

The preoperative diagnosis of pelvic masses has been elusive to date. Methods for characterization such as CA-125 have had limited specificity. We hypothesize that genomic variation can be used to create prediction models which accurately distinguish high grade serous ovarian cancer (HGSC) from benign tissue. Methods: In this retrospective, pilot study, we extracted DNA and RNA from HGSC specimens and from benign fallopian tubes. Then, we performed whole exome sequencing and RNA sequencing, and identified single nucleotide variants (SNV), copy number variants (CNV) and structural variants (SV). We used these variants to create prediction models to distinguish cancer from benign tissue. The models were then validated in independent datasets and with a machine learning platform. Results: The prediction model with SNV had an AUC of 1.00 (95% CI 1.00–1.00). The models with CNV and SV had AUC of 0.87 and 0.73, respectively. Validated models also had excellent performances. Conclusions: Genomic variation of HGSC can be used to create prediction models which accurately discriminate cancer from benign tissue. Further refining of these models (early-stage samples, other tumor types) has the potential to lead to detection of ovarian cancer in blood with cell free DNA, even in early stage.
Algorithms DNA Genomics Machine Learning Metastasis Mutation Ovarian Cancer RNA Tumors Benign Cancer Copy number Datasets Deoxyribonucleic acid Fallopian tubes Gene sequencing Multivariate analysis Nucleotides Prediction models Ribonucleic acid Tubes Variation

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