bims-ovdlit 2024-12-15 papers

bioRxiv. 2024 Dec 01. pii: 2024.11.28.625942. [Epub ahead of print]

Enriched Methylomes of Low-input and Fragmented DNA Using Fragment Ligation EXclusive Methylation Sequencing (FLEXseq).

Jingru Yu, Lauren S Ahmann, Yvette Y Yao, Wei Gu.

Methylome profiling is an emerging clinical tool for tumor classification and liquid biopsies. Here, we developed FLEXseq, a genome-wide methylation profiler that enriches and sequences the fragments of DNA flanking the CCGG motif. FLEXseq strongly correlates (Pearson's r = 0.97) with whole genome bisulfite sequencing (WGBS) while enriching 18-fold. To demonstrate the broad applicability of FLEXseq, we verified its usage across cells, body fluids, and formalin-fixed paraffin-embedded (FFPE) tissues. DNA dilutions down to 250 pg decreased CpG coverage, but bias in methylation remained low (Pearson's r ≥ 0.90) compared to a 10 ng input. FLEXseq offers a cost-efficient, base-pair resolution methylome with potential as a diagnostic tool for tissue and liquid biopsies.

DOI: https://doi.org/10.1101/2024.11.28.625942

Nat Methods. 2024 Dec;21(12): 2195-2196

Method of the Year 2024: spatial proteomics.

DOI: https://doi.org/10.1038/s41592-024-02565-3

Gynecol Oncol. 2024 Dec 12. pii: S0090-8258(24)01221-6. [Epub ahead of print]192 145-154

Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial.

OBJECTIVE: To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322).
METHODS: Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing. Multivariate analysis was performed. A p-value of 0.05 was considered significant. Progression-free survival (PFS) and overall survival (OS) were compared between groups defined by ctDNA kinetic profile. Cox survival model was used to search variables associated with PFS and OS. Kaplan-Mayer curve was used to graphically express the differences in PFS and OS. A log-rank test compared the two curves.
RESULTS: 188 patients were included. Blood samples were available for 168 patients at T0 and for 160 patients at T0 and T1 to assess ctDNA ratio kinetics. At T0, 107 patients (63.7 %) had detectable ctDNA. At T1, 137 (85.6 %) patients had negative ctDNA or a decrease of more than 80 %. There was a significant benefit in either PFS (p = 0.0017) or OS (p = 0.0036) in favor of early decrease of ctDNA ratio. A favorable decrease was associated with a greater likelihood of being able to perform CRS (OR: 3.94 (CI95 % 1.45-10.70), p = 0.0074).
CONCLUSIONS: Early decrease of ctDNA ratio can provide prognostic information early in the management of patients, allowing a more accurate information to patients and an early preparation for CRS (prehabilitation).

Keywords: Biomarker; Circulating tumor DNA; Epithelial ovarian cancer; Gynecologic oncology; Liquid biopsy; Next generation sequencing

DOI: https://doi.org/10.1016/j.ygyno.2024.12.004