Arjen R. Mensenkamp

Abstract Constitutional mismatch repair deficiency (CMMRD), caused by bi-allelic germline variants in mismatch repair (MMR) genes, is associated with high cancer incidence early in life. A better understanding of mutational processes driving sequential CMMRD tumors can advance optimal treatment. Here, we describe a genomic characterization on a representative collection of CMMRD-associated tumors consisting of 41 tumors from 17 individuals.

1 Introduction PTEN Hamartoma Tumor Syndrome (PHTS) is a rare hereditary syndrome caused by pathogenic germline variants in the phosphatase and tensin homolog (PTEN) gene. Estimates suggest PHTS might be as rare as 1:200 000 worldwide, although this likely is an underestimation [1, 2]. Current PHTS diagnostic guidelines consist of a complex system with multiple major and minor clinical criteria.

Abstract The development of multiple primary tumors is one of the hallmarks of hereditary cancer. The phenotypic presentation of individuals with multiple primary tumors is often heterogeneous, which hampers the establishment of a genetic diagnosis. The absence of a genetic diagnosis may lead to inappropriate surveillance advices and treatment choices.