Marc D. Tischkowitz

S4-Oligo: optimizing polygenic score methods for clinical deployment

This paper introduces S4-Oligo, an optimized polygenic score method for clinical use, which matches or exceeds existing models' accuracy while using fewer SNPs.

Using somatic data to aid germline clinical variant interpretation in developmental disorders

This paper uses somatic mutation data to improve the classification of germline variants in developmental disorders by identifying genes where somatic and germline mechanisms are concordant.

Genomic ascertainment of PALB2-related cancer predisposition

This study evaluates cancer risk and mortality in individuals with PALB2 pathogenic variants using genomic data from two cohorts, finding increased cancer odds and mortality.

A mouse model of PTEN Hamartoma Tumour Syndrome reveals that loss of the nuclear function of PTEN drives macrocephaly, lymphoid overgrowth, and late-onset cancer

This study shows that a specific PTEN mutation causes macrocephaly, lymphoid overgrowth, and late-onset cancer in mice by impairing nuclear PTEN functions, while maintaining normal PI3K/AKT signaling.

Analysis of BRCA1, BRCA2 and PALB2 related Fanconi anemia identifies scope to expand disease phenotypic features and predict breast cancer risk in heterozygotes

Breast cancer multigene germline panel testing in mainstream oncology based on clinical-public health utility (cancer mortality benefit): ESMO Precision Oncology Working Group recommendations

The paper recommends a standardized multigene germline panel for breast cancer patients based on cancer mortality benefit, including specific genes and excluding others.

Classification of Variants of Reduced Penetrance in High Penetrance Cancer Susceptibility Genes: Framework for Genetics Clinicians and Clinical Scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK)

The paper develops a framework for classifying variants of reduced penetrance in cancer susceptibility genes to improve variant interpretation consistency.

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants

The paper specifies gene-specific rules for interpreting ATM variants using ACMG/AMP guidelines, improving classification accuracy in a pilot study.

Incorporating alternative Polygenic Risk Scores into the BOADICEA breast cancer risk prediction model

This paper evaluates methods to incorporate alternative polygenic risk scores into the BOADICEA breast cancer risk prediction model, finding that retrospective likelihood approaches provide more accurate estimates.

Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1, updates to tumour pathology and cancer incidences.

This paper updates the BOADICEA cancer risk prediction model to include new genetic variants and continuous risk factors, improving risk reclassification for specific gene carriers.

The genetic analysis of a founder Northern American population of European descent identifies FANCI as a candidate familial ovarian cancer risk gene

This paper identifies FANCI c.1813C>T as a candidate familial ovarian cancer risk allele in a French Canadian population with founder effects.

A Comprehensive Epithelial Tubo-Ovarian Cancer Risk Prediction Model Incorporating Genetic and Epidemiological Risk Factors

The paper develops a multifactorial risk model for epithelial tubo-ovarian cancer incorporating genetic and epidemiological factors to stratify risk and guide screening.

The contribution of X-linked coding variation to severe developmental disorders

The paper analyzes X-linked coding variation in developmental disorders, finding similar rates in males and females and estimating pathogenicity of inherited variants.

VEP-G2P: A Tool for Efficient, Flexible and Scalable Diagnostic Filtering of Genomic Variants

VEP-G2P filters genomic variants for diagnostic purposes, showing higher sensitivity but lower precision for de novo and inherited variants, with significant background noise in controls.