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Personalized tumor-specific DNA junctions to detect circulating tumor in patients with endometrial cancer

Grassi, Tommaso ; Harris, Faye R ; Smadbeck, James B ; Murphy, Stephen J ; Block, Matthew S ; Multinu, Francesco ; Schaefer Klein, Janet L ; Zhang, Piyan ; Karagouga, Giannoula ; Liu, Minetta C ; Larish, Alyssa ; Lemens, Maureen A ; Sommerfield, Marla Kay S ; Cappuccio, Serena ; Cheville, John C ; Vasmatzis, George ; Mariani, Andrea Galli, Alvaro

PloS one, 2021-06, Vol.16 (6), p.e0252390-e0252390 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Personalized tumor-specific DNA junctions to detect circulating tumor in patients with endometrial cancer
Autor: Grassi, Tommaso ; Harris, Faye R ; Smadbeck, James B ; Murphy, Stephen J ; Block, Matthew S ; Multinu, Francesco ; Schaefer Klein, Janet L ; Zhang, Piyan ; Karagouga, Giannoula ; Liu, Minetta C ; Larish, Alyssa ; Lemens, Maureen A ; Sommerfield, Marla Kay S ; Cappuccio, Serena ; Cheville, John C ; Vasmatzis, George ; Mariani, Andrea
Galli, Alvaro
Assuntos: Analysis ; Biology and life sciences ; Biomarkers ; Cancer therapies ; Circulating Tumor DNA - blood ; Data analysis ; Deoxyribonucleic acid ; DNA ; Editing ; Endometrial cancer ; Endometrial Neoplasms - blood ; Endometrial Neoplasms - diagnosis ; Endometrial Neoplasms - pathology ; Endometrium ; Female ; Funding ; Genetic aspects ; Genomes ; Gynecology ; Humans ; Lymph nodes ; Lymphatic system ; Medicine ; Medicine and Health Sciences ; Methodology ; Mutation ; Obstetrics ; Oncology ; Ovarian cancer ; Patients ; Plasma ; Precision Medicine ; Research and Analysis Methods ; Research ethics ; Surgery ; Tumors ; Uterine cancer ; Uterus
É parte de: PloS one, 2021-06, Vol.16 (6), p.e0252390-e0252390
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors declare no competing financial interests.
These authors are joint senior authors on this work.
Descrição: There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer. Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated. CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer. This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study.
Editor: United States: Public Library of Science
Idioma: Inglês

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Personalized tumor-specific DNA junctions to detect circulating tumor in patients with endometrial cancer

United States: Public Library of Science

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