Biology subjects

Douville, C.

Publications and source records attributed to Douville, C..

5 recordsLinked to original sources

bioRxiv2025

Integrated Spatial Analysis of Ovarian Precancerous Lesions

Studying precancerous lesions is essential for improving early detection and prevention, particularly in aggressive cancers such as ovarian carcinoma. Here, we conducted integrated and spatial analyses of transcriptomes, aneuploidy, and clinic-pathological features in 166 ovarian precancerous lesions. Four pre-cancerous subtypes were identified transcriptomically: proliferative, immunoreactive, dormant, and mixed. These subtypes varied in their frequency of germline-BRCA1/2 mutations, aneuploidy, CCNE1/MYC amplification, proliferative activity, immune-regulatory gene expression, and histological features. Notably, the immunoreactive subtype upregulated immune-regulatory genes, exhibited chronic inflammation, and was enriched in cases with germline-BRCA1/2 mutations, deletions of chromosomes 17 (harboring TP53 and BRCA1) and 13 (harboring BRCA2), leading to a double "two-hit" involving TP53 and BRCA1/2. Tumor invasion was associated with the activation of interferon response pathways, epithelial-mesenchymal transition, and extracellular matrix remodeling. In summary, our results elucidate the earliest molecular landscape of ovarian precancerous lesions, serving as the foundation for future risk stratification to identify aggressive pre-cancerous lesions.

molecular biology↗

bioRxiv2019

Assessing aneuploidy with repetitive element sequencing.

We report a sensitive PCR-based assay that can detect aneuploidy in samples containing as little as 3 picograms of DNA. Using a single primer pair, we amplified [~]750,000 amplicons distributed throughout the genome Aneuploidy was detected in 49% of liquid biopsies from a total of 883 non-metastatic cancers of eight different types. Combining aneuploidy with somatic mutation detection and eight standard protein biomarkers yielded a median sensitivity of 80% at 99% specificity.

cancer biology↗

bioRxiv2017

Non-invasive detection of upper tract urothelial carcinomas through the analysis of driver gene mutations and aneuploidy in urine

Upper tract urothelial carcinomas (UTUC) of the renal pelvis or ureter can be difficult to detect and challenging to diagnose. Here, we report the development and application of a non-invasive test for UTUC based on molecular analyses of DNA recovered from cells shed into the urine. The test, called UroSEEK, incorporates assays for mutations in eleven genes frequently mutated in urologic malignancies and for allelic imbalances on 39 chromosome arms. At least one genetic abnormality was detected in 75% of urinary cell samples from 56 UTUC patients but in only 0.5% of 188 samples from healthy individuals. The assay was considerably more sensitive than urine cytology, the current standard-of-care. UroSEEK therefore has the potential to be used for screening or to aid in diagnosis in patients at increased risk for UTUC, such as those exposed to herbal remedies containing the carcinogen aristolochic acid.

cancer biology↗

bioRxiv2017

Non-invasive detection of bladder cancer through the analysis of driver gene mutations and aneuploidy

Current non-invasive approaches for bladder cancer (BC) detection are suboptimal. We report the development of non-invasive molecular test for BC using DNA recovered from cells shed into urine. This \"UroSEEK\" test incorporates assays for mutations in 11 genes and copy number changes on 39 chromosome arms. We first evaluated 570 urine samples from patients at risk for BC (microscopic hematuria or dysuria). UroSEEK was positive in 83% of patients that developed BC, but in only 7% of patients who did not develop BC. Combined with cytology, 95% of patients that developed BC were positive. We then evaluated 322 urine samples from patients soon after their BCs had been surgically resected. UroSEEK detected abnormalities in 66% of the urine samples from these patients, sometimes up to 4 years prior to clinical evidence of residual neoplasia, while cytology was positive in only 25% of such urine samples. The advantages of UroSEEK over cytology were particularly evident in low-grade tumors, wherein cytology detected none while UroSEEK detected 67% of 49 cases. These results establish the foundation for a new, non-invasive approach to the detection of BC in patients at risk for initial or recurrent disease.

cancer biology↗

bioRxiv2017

CRAVAT 4: Cancer-Related Analysis of Variants Toolkit

Cancer sequencing studies are increasingly comprehensive and well-powered, returning long lists of somatic mutations that can be difficult to sort and interpret. Diligent analysis and quality control can require multiple computational tools of distinct utility and producing disparate output, creating additional challenges for the investigator. The Cancer-Related Analysis of Variants Toolkit (CRAVAT) is an evolving suite of informatics tools for mutation interpretation that includes mutation projecting and quality control, impact prediction and extensive annotation, gene- and mutation-level interpretation including joint prioritization of all nonsilent consequence types, and structural and mechanistic visualization. Results from CRAVAT submissions are explored in an interactive, user-friendly web-environment with dynamic filtering and sorting designed to highlight the most informative mutation, even in the context of very large studies. CRAVAT can be run on a public web-portal, in the cloud, or downloaded for local use, and is easily integrated with other methods for cancer omics analysis.\n\nConflict of interestAll authors declare no potential conflict of interest.

bioinformatics↗