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Burçak Otlu

Publications and source records attributed to Burçak Otlu.

3 recordsLinked to original sources
PubMed2026

Identifying multigenic modules under selection in the tumor genome.

MOTIVATION: Genomic alterations in cancer arise from selective pressures acting on hallmark molecular modules, layered over a background of random mutagenic events. Methods to detect selection at the level of modules, as opposed to genes or nucleotides, are relatively underdeveloped. RESULTS: Here we present CanSRMaPP (Cancer Selection Recovery by Maximum Posterior Probability), a Bayesian model of the cancer genome that infers mutational selection on single genes and multi-genic modules while simultaneously modeling background events. Applying CanSRMaPP to lung adenocarcinoma genomes, we identify positive selection on 63 modules, yielding a model that parsimoniously explains the observed pattern of genetic alterations observed in new cancer cohorts. We further show that CanSRMaPP is adaptable to more tumor types and to alternative module definitions. We show that these modules serve as an effective scaffold for translating the cancer genome to molecular states, with prediction of cancer biomarker status as demonstration. AVAILABILITY: CanSRMaPP is freely available on GitHub. SUPPLEMENTARY INFORMATION: Supplementary Figs. S1-5, Supplementary Tables S1-5, and Supplementary Notes 1 and 2 are available at Bioinformatics online.

Journal Article↗
PubMed2026

Identification and validation of a previously missed mutational signature in colorectal cancer.

Mutational signature analysis has enhanced our understanding of mutagenic processes. In a recent study, we analyzed 802 microsatellite-stable colorectal cancers (CRC) and identified a de novo signature, SBS_D, which was decomposed into SBS18. Here, we re-evaluate this decomposition and provide evidence that SBS_D represents a distinct mutational process from SBS18. Through an analysis of 2,616 CRCs across three independent cohorts, we demonstrate that SBS_D is consistently present, suggesting this signature may have been previously overlooked. We illustrate that the pattern of SBS_D better aligns with signatures associated with deficiencies in DNA repair, despite evidence that SBS_D is not driven by canonical defects in these DNA repair pathways. Overall, this study identifies a previously unrecognized mutational signature in DNA repair-proficient CRC and proposes that its etiology may be linked to DNA repair infidelity emerging late in tumor development. SBS_D has been submitted to the COSMIC database and provisionally designated as SBS111.

Colorectal Neoplasms↗
PubMed2025

Identification and Validation of a Previously Missed Mutational Signature in Colorectal Cancer.

Mutational signature analysis has greatly enhanced our understanding of the mutagenic processes found in cancer and normal tissues. As part of a recent study, we analyzed 802 treatment-naïve, microsatellite-stable colorectal cancers (CRC) and identified a de novo signature, SBS_D, which was conservatively decomposed into SBS18, a signature associated with reactive oxygen species. Here, we re-evaluate this decomposition and provide evidence that SBS_D represents a distinct mutational process from that of SBS18. Through an independent analysis of 2,616 whole-genome sequenced microsatellite-stable CRCs across three distinct cohorts, we demonstrate that SBS_D is consistently present at a similar prevalence, suggesting that this signature may have been previously overlooked. Using a naïve decomposition approach, we demonstrate that the pattern of SBS_D better aligns with signatures previously associated with deficiencies in DNA polymerase delta (POLD1) proofreading and mismatch repair. However, multiple lines of evidence, including the absence of pathogenic mutations in the exonuclease domain of POLD1 or in mismatch repair-associated genes, indicate that SBS_D is not driven by canonical defects in these DNA repair pathways. Overall, this study identifies a previously unrecognized mutational signature in microsatellite-stable CRC and proposes that its etiology may be linked to DNA repair infidelity emerging late in tumor development in samples without canonical defects in DNA repair pathways.

Journal Article↗