bims-ovdlit 2022-09-04 papers

Issue of 2022–09–04
three papers selected by
Lara Paracchini, Humanitas Research

Acta Biomed. 2022 Aug 31. 93(4): e2022051

A prospective multicentric study of risk-reducing salpingo-oophorectomy in BRCA mutation patients.

Vera Loizzi, Ettore Cicinelli, Vittoria Del Vecchio, Francesca Arezzo, Xheni Deromemaj, Anila Kardhashi, Angelo Paradiso, Francesco Legge, Maria Iole Natalicchio, Leonardo Resta, Nicoletta Resta, Daria Carmela Loconte, Gennaro Cormio.

BACKGROUND AND AIM OF THE WORK: BRCA1/2 are tumour-suppressor genes involved in DNA homologous recombination and ovarian cancer development. The study evaluated the risk of tumor cancer in women presenting the BRCA mutations.
METHODS: Risk-reducing surgery (RRS) was performed in 100 patients carrying BRCA1 (aged between 30-73 years, median age was 51 years) and BRCA 2 mutation (aged between 36-70 years, median age was 53 years). Fifty-eight patients had previous history of breast cancer.
RESULTS: Between the 100 patients, 82 women underwent risk-reducing salpingo-oophorectomy (RRSO) through a laparoscopic minimally invasive approach, 7 (7 %) underwent laparoscopic RRSO and contextual hysterectomy, 1 woman (1 %) underwent RRSO through a laparotomic approach and 10 women (10 %) laparotomic RRSO and hysterectomy. During 5 (5 %) laparoscopic RRSO, prophylactic bilateral mastectomy was also performed. Early and late complication occurred in 3 patients (3 %). Two patients (2 %) were found to have occult Serous Tubal Intraepithelial Carcinoma (STIC) and three patients (3 %) occult cancer.
CONCLUSIONS: RRSO is safe and feasible in BRCA mutation carriers. The procedure is effective for genetic prevention of ovarian cancer.

DOI: https://doi.org/10.23750/abm.v93i4.11695

J Hematol Oncol. 2022 Sep 02. 15(1): 125

Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients.

Ariane Hallermayr, Tobias Wohlfrom, Verena Steinke-Lange, Anna Benet-Pagès, Florentine Scharf, Ellen Heitzer, Ulrich Mansmann, Christopher Haberl, Maike de Wit, Holger Vogelsang, Markus Rentsch, Elke Holinski-Feder, Julia M A Pickl.

BACKGROUND: Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients. Untargeted cfDNA analysis using whole-genome sequencing (WGS) does not need a priori knowledge of the patient´s mutation profile.
METHODS: Here we established LIquid biopsy Fragmentation, Epigenetic signature and Copy Number Alteration analysis (LIFE-CNA) using WGS with ~ 6× coverage for detection of circulating tumor DNA (ctDNA) in CRC patients as a marker for CRC detection and monitoring.
RESULTS: We describe the analytical validity and a clinical proof-of-concept of LIFE-CNA using a total of 259 plasma samples collected from 50 patients with stage I-IV CRC and 61 healthy controls. To reliably distinguish CRC patients from healthy controls, we determined cutoffs for the detection of ctDNA based on global and regional cfDNA fragmentation patterns, transcriptionally active chromatin sites, and somatic copy number alterations. We further combined global and regional fragmentation pattern into a machine learning (ML) classifier to accurately predict ctDNA for cancer detection. By following individual patients throughout their course of disease, we show that LIFE-CNA enables the reliable prediction of response or resistance to treatment up to 3.5 months before commonly used CEA.
CONCLUSION: In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of all CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring. Trial registration DRKS00012890.

Keywords: Chromatin signatures; Colorectal cancer; Liquid biopsy; Somatic copy number alterations; Whole-genome sequencing; cfDNA fragmentation; ctDNA

DOI: https://doi.org/10.1186/s13045-022-01342-z

Explor Target Antitumor Ther. 2020 ;1(6): 434-451

Circulating biomarkers in malignant pleural mesothelioma.

Giuseppe Viscardi, Davide Di Natale, Morena Fasano, Marta Brambilla, Riccardo Lobefaro, Alessandro De Toma, Giulia Galli.

Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.

Keywords: CTC; Mesothelioma; biomarkers; ctDNA; liquid biopsy; malignant pleural mesothelioma; mesothelin; miRNAs

DOI: https://doi.org/10.37349/etat.2020.00028