bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2024–04–07
four papers selected by
Lara Paracchini, Humanitas Research
  1. FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.
  2. Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.
  3. Sensitive circulating tumor DNA-based residual disease detection in epithelial ovarian cancer.
  4. Editorial for familial cancer: cascade genetic testing.
  1. Nat Commun. 2024 Mar 30. 15(1): 2790
    FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.
    Yaping Liu, Sarah C Reed, Christopher Lo, Atish D Choudhury, Heather A Parsons, Daniel G Stover, Gavin Ha, Gregory Gydush, Justin Rhoades, Denisse Rotem, Samuel Freeman, David W Katz, Ravi Bandaru, Haizi Zheng, Hailu Fu, Viktor A Adalsteinsson, Manolis Kellis.
      Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.
    DOI:  https://doi.org/10.1038/s41467-024-47196-6
  2. Cell Oncol (Dordr). 2024 Apr 02.
    Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.
    Regine Marlin, Jean-Samuel Loger, Clarisse Joachim, Coralie Ebring, Guillaume Robert-Siegwald, Sabrina Pennont, Mickaelle Rose, Kevin Raguette, Valerie Suez-Panama, Sylviane Ulric-Gervaise, Sylvie Lusbec, Odile Bera, Alexis Vallard, Aude Aline-Fardin, Emeline Colomba, Mehdi Jean-Laurent.
       PURPOSE: Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases.
    METHODS: We conducted a comprehensive pangenomic analysis to categorize the copy number alterations involved in these tumors. Whole-Exome Sequencing (WES) and Homologous Recombination (HR) analysis were performed. The alterations obtained from the WES were classified into various signatures using the Copy Number Signatures tool available in COSMIC.
    RESULTS: We identified several signatures that correlated with tumor stage and disctinct prognoses. These signatures all seem to be linked to replication stress, with CCNE1 amplification identified as the primary driver of oncogenesis in over 70% of tumors analyzed.
    CONCLUSION: The identification of CCNE1 amplification, which is currently being explored as a therapeutic target in clinical trials, suggests new treatment strategies for high-grade endometrial cancer. This finding holds particular significance for Martinique, where access to care is challenging.
    Keywords:   CCNE1 amplification; Copy number signature; High-grade endometrial cancer; Replication stress
    DOI:  https://doi.org/10.1007/s13402-024-00942-w
  3. Life Sci Alliance. 2024 Jun;pii: e202402658. [Epub ahead of print]7(6):
    Sensitive circulating tumor DNA-based residual disease detection in epithelial ovarian cancer.
    Heini Ml Kallio, Kalle Savolainen, Tuomo Virtanen, Lauri Ryyppö, Hanna Selin, Päivi Martikainen, Synnöve Staff, Kati Kivinummi, Joonatan Sipola, Juuso Vuorinen, Jussi Nikkola, Matti Nykter, Annika Auranen, Matti Annala.
      Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)-based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1,195 control samples. ctDNA was detected in 51 of 55 (93%) samples at diagnosis, and 18 of 18 (100%) samples at progression. Positive ctDNA in the last on-treatment sample was associated with rapid progression (median 1.02 versus 3.38 yr, HR = 5.63, P < 0.001) and reduced overall survival (median 2.31 versus NR yr, HR = 8.22, P < 0.001) in patients with high-grade serous cancer. In the case of 12 patients, ctDNA assays detected progression earlier than standard surveillance, with a median lead time of 5.9 mo. To approach the physical limits of ctDNA detection, five patients were analyzed using ultra-sensitive assays interrogating 479-1,856 tumor mutations, capable of tracking ctDNA fractions down to 0.0004%. Our results demonstrate that ctDNA assays achieve high sensitivity and specificity in detecting post-operative residual disease in EOC.
    DOI:  https://doi.org/10.26508/lsa.202402658
  4. Fam Cancer. 2024 Apr 01.
    Editorial for familial cancer: cascade genetic testing.
    Maria Katapodi, Joanne Ngeow, Yuen Yie, Melissa Frey.
      
    DOI:  https://doi.org/10.1007/s10689-024-00378-z
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