bims-ovdlit 2022-01-16 papers

Aust Prescr. 2021 Dec;44(6): 208-209

Niraparib for ovarian cancer.

DOI: https://doi.org/10.18773/austprescr.2021.059

Ann Oncol. 2022 Jan 08. pii: S0923-7534(22)00004-7. [Epub ahead of print]

Homologous recombination deficiency testing in first-line ovarian cancer.

K N Moore, A du Bois.

DOI: https://doi.org/10.1016/j.annonc.2021.12.013

Am J Med Genet A. 2022 Feb;188(2): 393-394

Genome-Wide Cell-Free DNA Screening Tests Go Beyond Scope of Traditional cfDNA Assays.

DOI: https://doi.org/10.1002/ajmg.a.62274

Nature. 2022 Jan 12.

Important genomic regions mutate less often than do other regions.

Jianzhi Zhang.

Keywords: Epigenetics; Evolution; Genetics; Genomics

DOI: https://doi.org/10.1038/d41586-022-00017-6

Cancers (Basel). 2021 Dec 21. pii: 4. [Epub ahead of print]14(1):

Prognostic Significance of SLFN11 Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer.

Victoria Tserpeli, Dimitra Stergiopoulou, Dora Londra, Lydia Giannopoulou, Paul Buderath, Ioanna Balgkouranidou, Nikolaos Xenidis, Christina Grech, Eva Obermayr, Robert Zeillinger, Kitty Pavlakis, Theodoros Rampias, Stylianos Kakolyris, Sabine Kasimir-Bauer, Evi S Lianidou.

BACKGROUND: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment.
METHODS: In the present study, we examined the methylation status of six gene promoters (BRCA1, CST6, MGMT, RASSF10, SLFN11 and USP44) in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC.
RESULTS: We report for the first time that the DNA methylation of SLFN11 in plasma cfDNA was significantly correlated with worse PFS (p = 0.045) in advanced stage HGSOC.
CONCLUSIONS: Our results strongly indicate that SLFN11 epigenetic inactivation could be a predictor of resistance to platinum drugs in ovarian cancer. Our results should be further validated in studies based on a larger cohort of patients, in order to further explore whether the DNA methylation of SLFN11 promoter could serve as a potential prognostic DNA methylation biomarker and a predictor of resistance to platinum-based chemotherapy in ovarian cancer.

Keywords: DNA methylation; Schlaffen11; high-grade serous ovarian cancer; liquid biopsy; methylation specific PCR; plasma cell-free DNA; prognostic biomarker; progression free survival

DOI: https://doi.org/10.3390/cancers14010004

Br J Cancer. 2022 Jan 11.

Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy.

Jie Sun, Congcong Yan, Dandan Xu, Zicheng Zhang, Ke Li, Xiaobo Li, Meng Zhou, Dapeng Hao.

BACKGROUND: Immunotherapy has revolutionised the field of cancer therapy and immunology, but has demonstrated limited therapeutic efficacy in high-grade serous ovarian cancer (HGSOC).
METHODS: Multi-omics data of 495 TCGA HGSOC tumours and RNA-seq data of 1708 HGSOC tumours were analyzed. Multivariate Cox regression analysis and meta-analyses were used to identify prognostic genes. The immune microenvironment was characterised using the ssGSEA methods for 28 immune cell types. Immunohistochemistry staining of tumour tissues of 14 patients was used to validate the key findings further.
RESULTS: A total of 1142 genes were identified as favourable prognostic genes, which are prevailing in immune-related pathways and the infiltration of most immune subpopulations was observed to be associated with a favourable prognosis suggesting that tumour immunogenicity was the most prominent factor associated with improved clinical outcomes and response to chemotherapy of HGSOC. We identified multiple genomic and transcriptomic determinants of immunogenicity, including the copy loss of chromosome 4q and deficiencies of the homologous recombination pathway. Finally, an immunological subtype characterised by increased infiltration of activated CD8 T cells and decreased Tregs was associated with favourable prognosis and improved therapeutic efficacy.
CONCLUSIONS: Our study characterised the immunogenomic landscape and refined the immunological classifications of HGSOC. This may improve the selection of patients with HGSOC who are suitable candidates for immunotherapy.

DOI: https://doi.org/10.1038/s41416-021-01692-4

Br J Cancer. 2022 Jan 10.

Delivering on the promise of early detection with liquid biopsies.

David Crosby.

Liquid biopsy approaches are relatively well developed for cancer therapy monitoring and disease relapse, but they also have incredible potential in the cancer early detection and screening field. There are, however, several challenges to overcome before this potential can be met. Research in this area needs to be cohesive and, as a driver of research, Cancer Research UK is in an ideal position to enable this.

DOI: https://doi.org/10.1038/s41416-021-01646-w