bims-ovdlit 2024-11-24 papers

Nat Commun. 2024 Nov 20. 15(1): 10053

Author Correction: Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma.

Andrea Flesken-Nikitin, Coulter Q Ralston, Dah-Jiun Fu, Andrea J De Micheli, Daryl J Phuong, Blaine A Harlan, Christopher S Ashe, Amanda P Armstrong, David W McKellar, Sangeeta Ghuwalewala, Lora H Ellenson, John C Schimenti, Benjamin D Cosgrove, Alexander Yu Nikitin.

DOI: https://doi.org/10.1038/s41467-024-54465-x

Int Rev Cell Mol Biol. 2024 ;pii: S1937-6448(24)00026-1. [Epub ahead of print]383 xi-xv

Epigenetic regulation of cancer.

Sheila Spada, Lorenzo Galluzzi.

DOI: https://doi.org/10.1016/S1937-6448(24)00026-1

Carcinogenesis. 2024 Nov 16. pii: bgae073. [Epub ahead of print]

Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing. A systematic review and patient-level survival data meta-analysis.

Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi.

Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of plasma cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess circulating tumor DNA (ctDNA) fraction. This meta-analysis aims to summarize the current findings and comprehensively investigate the prognostic value of baseline ctDNA detected by ULP-WGS in solid tumors. A systematic review was carried out by searching PubMed/MEDLINE and Scopus databases to identify eligible studies conducted between January 2014 and January 2024. Inclusion criteria comprised studies with reported overall survival (OS) and progression-free survival (PFS) outcomes across therapy-naïve patients with different solid tumors. All patients underwent baseline ULP-WGS of plasma cfDNA and were categorized as ctDNA positive (tumor fraction ≥10%) or negative (tumor fraction <10%). A one-stage meta-analysis was performed using patient-level survival data reconstructed from published articles. A Cox proportional hazards model with shared frailty was used to assess the difference in survival between arms. A total of six studies, comprising 620 patients (367 negative ctDNA and 253 positive ctDNA), were included in the OS analysis, while five studies, involving 349 patients (212 negative ctDNA and 137 positive ctDNA), were included in the PFS analysis. The meta-analysis showed that patients with baseline positive ctDNA had a significantly higher risk of death (HR = 2.60, 95% CI: 2.01-3.36) and disease progression (HR = 2.28, 95% CI: 1.71-3.05) compared to those with negative ctDNA. The presence of a positive ctDNA at baseline is associated with increased risk of death and progression in patients with same stage cancer.

Keywords: Circulating tumor DNA; Whole Genome Sequencing; overall survival; patient level meta-analysis; progression-free survival

DOI: https://doi.org/10.1093/carcin/bgae073

Clin Cancer Res. 2024 Nov 19.

Analysis of shared variants between cancer biospecimens.

PURPOSE: Mutational data from multiple solid and liquid biospecimens of a single patient is often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence.
EXPERIMENTAL DESIGN: Utilizing 8,000 patient tumors from The Cancer Genome Atlas (TCGA) across 33 cancer types, we estimated background rates of co-occurrence rates of mutations between discrete pairs of samples across cancers and by cancer type. We developed a mutational profile similarity score (MPS) that uses a large background database to produce confidence estimates that two tumors share a unique, related molecular profile. The MPS algorithm was applied to randomly paired tumor profiles, including patients who underwent repeat solid tumor biopsies sequenced with MSK-IMPACT (n=53,113). We also evaluated the MPS in sample pairs from single patients with multiple cancers (n=2,012), as well as patients with plasma and solid-tumor variant profiles (n=884 patients).
RESULTS: In unrelated tumors, nucleotide-specific variants are shared in 1.3% (cancer-type agnostic) and in 10-13% (cancer-type specific) of cases. The mutational profile similarity (MPS) method contextualized shared variants to specify whether patients had a single cancer versus multiple distinct cancers. When multiple tumors were compared from the same patient, and an initial clinicopathologic diagnosis was discordant with molecular findings, the MPS anticipated future diagnosis changes in 28% of examined cases.
CONCLUSIONS: Use of a novel shared variant framework can provide information to clarify the molecular relationship between compared biospecimens with minimal required input.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-1583

Nat Genet. 2024 Nov 20.

Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations.

The prevalence and nature of somatic copy number alterations (CNAs) in breast epithelium and their role in tumor initiation and evolution remain poorly understood. Using single-cell DNA sequencing (49,238 cells) of epithelium from BRCA1 and BRCA2 carriers or wild-type individuals, we identified recurrent CNAs (for example, 1q-gain and 7q, 10q, 16q and 22q-loss) that are present in a rare population of cells across almost all samples (n = 28). In BRCA1/BRCA2 carriers, these occur before loss of heterozygosity (LOH) of wild-type alleles. These CNAs, common in malignant tumors, are enriched in luminal cells but absent in basal myoepithelial cells. Allele-specific analysis of prevalent CNAs reveals that they arose by independent mutational events, consistent with convergent evolution. BRCA1/BRCA2 carriers contained a small percentage of cells with extreme aneuploidy, featuring loss of TP53, BRCA1/BRCA2 LOH and multiple breast cancer-associated CNAs. Our findings suggest that CNAs arising in normal luminal breast epithelium are precursors to clonally expanded tumor genomes.

DOI: https://doi.org/10.1038/s41588-024-01988-0