Esposito, Giuseppina (2023) Development and validation of a non-invasive screening and diagnosis test for endometrial cancer through the new Next Generation Sequencing techniques of the circulating tumor DNA (Liquid Biopsy). [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Development and validation of a non-invasive screening and diagnosis test for endometrial cancer through the new Next Generation Sequencing techniques of the circulating tumor DNA (Liquid Biopsy). |
| Autori: | Autore Email Esposito, Giuseppina giusyesposito890@gmail.com |
| Data: | 12 Dicembre 2023 |
| Numero di pagine: | 30 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Sanità Pubblica |
| Dottorato: | Sanità pubblica e medicina preventiva |
| Ciclo di dottorato: | 35 |
| Coordinatore del Corso di dottorato: | nome email Triassi, Maria triassi@unina.it |
| Tutor: | nome email Di Spiezio Sardo, Attilio [non definito] |
| Data: | 12 Dicembre 2023 |
| Numero di pagine: | 30 |
| Parole chiave: | endometrial cancer; liquid biopsy, cfDNA, atypical hyperplasia, conservative treatment |
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/40 - Ginecologia e ostetricia Area 06 - Scienze mediche > MED/42 - Igiene generale e applicat |
| Depositato il: | 19 Dic 2023 09:28 |
| Ultima modifica: | 09 Apr 2025 13:24 |
| URI: | http://www.fedoa.unina.it/id/eprint/14987 |
Abstract
There is currently no blood-based marker in routine use for endometrial cancer patients. Such a marker could potentially be used for early detection, but it could also help to track tumor recurrence following hysterectomy. This study was designed to determine if tumor-associated mutations could be detected in cell-free DNA from the peripheral blood of endometrial carcinoma or atypical hyperplasia patients. Next-generation sequencing was performed on cell-free DNA extracted from plasma obtained from a peripheral blood draw at the time of hysterectomy/hysteroscopy and the matching tumor DNA from 85 patients with endometrial carcinomas or atypical hyperplasia. At least one pathogenic mutation in plasma samples was detected in 70/77 (94%) of the tumors analyzed, the detected mutation on plasma was the same of the one detected in solid tumor in 50/77 (65%) of cases. The cfDNA expression in plasma do not relate with grading (p>0,05) but is associated with myometrial infiltration (chi-square 25; p=0,001). The presence of cfDNA mutation of PTEN (chi-square 25; p<0,001) and PIK3RI (chi square 22; p<0,001) in plasma related with grading G3 and >50% infiltration. The presence of cfDNA mutation of CTCF (chi-square 12; p<0,01) and BRAF (chi square 18; p<0,001) related with >50% infiltration. ZFHX3, P53, PTEN was associated with diagnosis of endometrioid cancer while KMT2C was associated with atypical hyperplasia. These results demonstrate that mutations in genes relevant to endometrial cancer can be identified in the peripheral blood of patients at the time of surgery or of hysteroscopy for patient who undergo conservative management. Future studies can help to determine the post-operative time course of mutation clearance from the peripheral blood and if mutation re-emergence is predictive of recurrence.
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