bims-ovdlit 2021-10-31 papers

Issue of 2021–10–31
four papers selected by
Lara Paracchini, Humanitas Research

BMC Cancer. 2021 Oct 28. 21(1): 1154

Homologous recombination proficiency in ovarian and breast cancer patients.

Justin Fortune Creeden, Nisha S Nanavaty, Katelyn R Einloth, Cassidy E Gillman, Laura Stanbery, Danae M Hamouda, Lance Dworkin, John Nemunaitis.

Homologous recombination and DNA repair are important for genome maintenance. Genetic variations in essential homologous recombination genes, including BRCA1 and BRCA2 results in homologous recombination deficiency (HRD) and can be a target for therapeutic strategies including poly (ADP-ribose) polymerase inhibitors (PARPi). However, response is limited in patients who are not HRD, highlighting the need for reliable and robust HRD testing. This manuscript will review BRCA1/2 function and homologous recombination proficiency in respect to breast and ovarian cancer. The current standard testing methods for HRD will be discussed as well as trials leading to approval of PARPi's. Finally, standard of care treatment and synthetic lethality will be reviewed.

Keywords: BRCA; Breast cancer; Homologous recombination; Homologous recombination deficient; Homologous recombination proficient; Ovarian cancer; PARP inhibitor

DOI: https://doi.org/10.1186/s12885-021-08863-9

Front Med (Lausanne). 2021 ;8 748668

Feasibility of Droplet Digital PCR Analysis of Plasma Cell-Free DNA From Kidney Transplant Patients.

Barbara Jerič Kokelj, Maja Štalekar, Sebastian Vencken, David Dobnik, Polona Kogovšek, Matjaž Stanonik, Miha Arnol, Maja Ravnikar.

Increasing research demonstrates the potential of donor-derived cell-free DNA (dd-cfDNA) as a biomarker for monitoring the health of various solid organ transplants. Several methods have been proposed for cfDNA analysis, including real-time PCR, digital PCR, and next generation sequencing-based approaches. We sought to revise the droplet digital PCR (ddPCR)-based approach to quantify relative dd-cfDNA in plasma from kidney transplant (KTx) patients using a novel pilot set of assays targeting single nucleotide polymorphisms that have a very high potential to distinguish cfDNA from two individuals. The assays are capable of accurate quantification of down to 0.1% minor allele content when analyzing 165 ng of human DNA. We found no significant differences in the yield of extracted cfDNA using the three different commercial kits tested. More cfDNA was extracted from the plasma of KTx patients than from healthy volunteers, especially early after transplantation. The median level of donor-derived minor alleles in KTx samples was 0.35%. We found that ddPCR using the evaluated assays within specific range is suitable for analysis of KTx patients' plasma but recommend prior genotyping of donor DNA and performing reliable preamplification of cfDNA.

Keywords: assay evaluation; droplet digital PCR; graft health monitoring; kidney transplantation; minor allele quantification; plasma cell-free DNA

DOI: https://doi.org/10.3389/fmed.2021.748668

BMC Res Notes. 2021 Oct 24. 14(1): 394

Repeatability of methylation measures using a QIAseq targeted methyl panel and comparison with the Illumina HumanMethylation450 assay.

Chenglong Yu, Pierre-Antoine Dugué, James G Dowty, Fleur Hammet, JiHoon E Joo, Ee Ming Wong, Mahnaz Hosseinpour, Graham G Giles, John L Hopper, Tu Nguyen-Dumont, Robert J MacInnis, Melissa C Southey.

OBJECTIVE: In previous studies using Illumina Infinium methylation arrays, we have identified DNA methylation marks associated with cancer predisposition and progression. In the present study, we have sought to find appropriate technology to both technically validate our data and expand our understanding of DNA methylation in these genomic regions. Here, we aimed to assess the repeatability of methylation measures made using QIAseq targeted methyl panel and to compare them with those obtained from the Illumina HumanMethylation450 (HM450K) assay. We included in the analysis high molecular weight DNA extracted from whole blood (WB) and DNA extracted from formalin-fixed paraffin-embedded tissues (FFPE).
RESULTS: The repeatability of QIAseq-methylation measures was assessed at 40 CpGs, using the Intraclass Correlation Coefficient (ICC). The mean ICCs and 95% confidence intervals (CI) were 0.72 (0.62-0.81), 0.59 (0.47-0.71) and 0.80 (0.73-0.88) for WB, FFPE and both sample types combined, respectively. For technical replicates measured using QIAseq and HM450K, the mean ICCs (95% CI) were 0.53 (0.39-0.68), 0.43 (0.31-0.56) and 0.70 (0.59-0.80), respectively. Bland-Altman plots indicated good agreement between QIAseq and HM450K measurements. These results demonstrate that the QIAseq targeted methyl panel produces reliable and reproducible methylation measurements across the 40 CpGs that were examined.

Keywords: Bland–Altman plot; DNA methylation; Formalin-fixed paraffin-embedded; Illumina Infinium methylation arrays; Intraclass correlation coefficient; Targeted bisulphite sequencing; Whole blood

DOI: https://doi.org/10.1186/s13104-021-05809-z

In Vivo. 2021 Nov-Dec;35(6):35(6): 3613-3622

Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma.

Hyunjin Kim, Go Eun Bae, Yoon Yang Jung, Hyun-Soo Kim.

BACKGROUND/AIM: We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC).
CASE REPORT: A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA.
CONCLUSION: Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.

Keywords: Ovary; high-grade serous carcinoma; mesonephric-like adenocarcinoma; serous tubal intraepithelial carcinoma; tubal intraepithelial metastasis

DOI: https://doi.org/10.21873/invivo.12667