Genetic factors in colorectal cancer

LynchRisk: a Bayesian network to estimate the probability of Lynch syndrome based on pedigree and tumor characteristics

LynchRisk estimates Lynch syndrome probability using pedigree, cancer history, and tumor MMR status through a Bayesian model.

Inflammation is an essential trigger for POLE-driven ultramutated colorectal cancer

This study shows that inflammation triggers POLE-mutant colorectal cancer in mice, revealing inflammation as a key driver and establishing a preclinical model for drug discovery.

TP53 status aligns with morphology and metaplastic programs in colorectal cancer organoids, and MDM2 P2 promoter usage reflects p53 activity

This study links TP53 status to morphology and metaplastic programs in CRC organoids, showing P2 promoter usage reflects p53 activity beyond genotype in some cases.

Heterozygous germline MSH3 mutations, and probably MLH3 mutations, act as classical tumour suppressors, leading to excess somatic deletion mutations, signature ID4 and increased colorectal cancer risk

Hunting for microsatellite instability in long-read data with Owl

Owl quantifies microsatellite instability from long-read data, identifying MSI-high genomes and motif-specific patterns in cancer samples.

Prevalence of Colorectal Cancer Molecular Profiles Is Not Captured by a Single Age Threshold

This study shows that age thresholds do not accurately capture molecular profile prevalence in colorectal cancer, finding non-linear and opposing age trajectories for different profiles.

Multidimensional mutational phenotypes of MMR deficiency in human cancer cells

This study maps the mutational consequences of MMR gene deficiencies in cancer cells using CRISPR, mutation accumulation, and whole-genome sequencing, revealing multidimensional mutational phenotypes.

Differential causative effects of germline pathogenic variants in MUTYH and PALB2 in a patient with colorectal polyposis and breast cancer

The paper investigates the differential contributions of MUTYH and PALB2 germline variants to colorectal polyposis and breast cancer using mutational signatures in a single patient.

Tracing the stemness and malignant transition in a heritable colorectal cancer Lynch Syndrome by single-cell RNA-seq analysis

This paper uses single-cell RNA sequencing to analyze cellular changes in Lynch Syndrome colorectal cancer, identifying cancer stem cells, immune infiltration, and mutation burden during malignant transition.

MAIT cell enrichment in Lynch syndrome is associated with immune surveillance and colorectal cancer risk

The paper identifies MAIT cell enrichment in Lynch syndrome carriers without CRC, linked to immune surveillance and reduced cancer risk.

Stress-Survival Pathway Profiling Reveals MCM10 as a Candidate Biomarker of Hispanic Colorectal Cancer Disparities

This study identifies MCM10 as a potential biomarker for CRC disparities in Hispanics by analyzing stress-survival pathway gene expression and functional roles in tumor progression.

MSIanalyzer: Targeted Nanopore Sequencing Enables Single Nucleotide Resolution Analysis of Microsatellite Instability Diversity

MSIanalyzer uses targeted nanopore sequencing to analyze microsatellite instability at single-nucleotide resolution, revealing distinct repeat profiles and allelic diversity in cancer cell lines.

Colibactin-associated mutations in the human colon appear to reflect anatomy and early exposure, not oncogenesis

The paper analyzes mutations in colon crypts to determine if colibactin is linked to early-onset CRC, finding that its association reflects anatomy rather than oncogenesis.

Single-crypt evolutionary trajectories of human sporadic and hereditary colorectal precancers

This study compares the genomic evolution of sporadic and hereditary colorectal precancers using single-crypt whole-genome sequencing, revealing distinct mutation patterns and evolutionary trajectories.

DNA methylation signatures of mismatch repair-deficient colorectal cancer

This study identifies DNA methylation differences between microsatellite stable and microsatellite instable colorectal cancers, revealing MLH1-independent markers of mismatch repair deficiency and the impact of anatomical location.

Analysis of Microsatellite Instability Intensity in Single-Cell Resolution with scMnT reveals Tumor Heterogeneity in Colorectal Cancer

This study introduces scMnT, a method to quantify microsatellite instability (MSI) intensity at single-cell resolution in colorectal cancer, revealing heterogeneity and associations with immunotherapy response and cell origin.

Reference-free microsatellite instability detection from tumor sequencing using intrasample variability modeling

PROMIS detects microsatellite instability in tumor sequencing without reference data or matched normals, achieving high accuracy across multiple cancer types and sample types.

Intratumoral heterogeneity in microsatellite instability at single cell resolution

The paper investigates intratumoral heterogeneity in microsatellite instability (MSI) using single-cell sequencing data, finding evidence of MSI status variation within tumors classified as MSI-H or MSS.

Global Proteomic Analysis of Colorectal Cancers Stratified by Microsatellite Instability Subtype Reveals Protein Differences

This study performs a global proteomic analysis of colorectal cancers stratified by microsatellite instability subtype, revealing protein differences associated with Lynch syndrome and other subtypes.

Insights into the causes and consequences of DNA repeat expansions from 700,000 biobank participants

The paper analyzes DNA repeat instability in 700,000 participants to identify genetic modifiers of repeat expansion and contraction rates and their clinical associations.

On-target mutations confer resistance to WRN helicase inhibitors in Microsatellite Unstable Cancer Cells.

This study identifies on-target WRN mutations as resistance mechanisms in MSI cancer cells to WRN helicase inhibitors and suggests combination therapies to prevent resistance.

Genetically induced mouse model for colon-specific epithelial cell tumorigenesis driven by loss of K8 and Apc

This study develops a genetic, colon-specific mouse model of colorectal cancer driven by K8 and Apc loss, showing increased tumorigenesis and reduced K8 expression in human patients.

MSICKB: A Curated Knowledgebase for Exploring Molecular Heterogeneity and Biomarker Discovery in Microsatellite Instability Cancers

MSICKB curates MSI-related data from 492 publications to characterize molecular heterogeneity and identify biomarkers for precision oncology in MSI cancers.

Germline haploinsufficiency for the base excision repair gene MUTYH causes mutational signature SBS18 in multiple tumour types, specifically leading to an increased risk of colorectal cancer

This study shows that germline MUTYH haploinsufficiency increases mutational signature SBS18 and CRC risk, but not other cancers, due to oxidative DNA damage in the colorectum.

Artificial Intelligence Reveals Prognostic TP53 Pathway Alterations in FOLFOX-Treated Early-Onset Colorectal Cancer Among Populations at Risk

The paper uses AI to analyze genomic data from colorectal cancer patients, finding TP53 pathway alterations are linked to better survival in Hispanic/Latino patients treated with FOLFOX.

Constrained hypermutation and absence of TERT promoter mutations in Lynch syndrome-associated urothelial cancer

This study analyzes the somatic mutation landscape of Lynch syndrome-associated urothelial cancer and finds a lack of TERT promoter mutations and a distinct mutation profile.

APC I1307K and clinical management: insights from UK Biobank association analysis of colorectal and other cancer risks in Ashkenazi and non-Ashkenazi whites

The paper analyzes UK Biobank data to assess the association of APC I1307K variant with colorectal cancer risk in Ashkenazi and non-Ashkenazi whites, finding no significant association and highlighting the need for larger studies.

Saturation mapping of MUTYH variant effects using DNA repair reporters

The paper maps the functional effects of MUTYH variants using deep mutational scanning and DNA repair reporters, resolving variants of uncertain significance and identifying risk-associated mutations.

Unusual profile of germline genetic variants in unselected colorectal cancer patients from a high-prevalence region in Panama

The study identifies germline genetic variants in 95 Panamanian colorectal cancer patients, finding 10% with pathogenic variants in MUTYH, CHEK2, and other genes, but no mutations in mismatch repair genes.

Clinical syndromes linked to biallelic germline variants in MCM8 and MCM9

This study identifies biallelic germline variants in MCM8 and MCM9 as linked to polyposis, gastric cancer, early-onset colorectal cancer, and hypogonadism, with MCM9 variants showing stronger associations.