Exploring_the_landscape_of_somatic_mutations_in_normal_tissue_GI_LYNCH___WGS

Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.

Type: Whole Genome Sequencing
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008092	Lynch Syndrome (LS) is an autosomal dominant disease conferring a high risk of colorectal cancer due to germline heterozygous mutations in a DNA mismatch repair (MMR) gene. Although cancers in LS patients show elevated somatic mutation burdens, information on mutation rates in normal tissues and understanding of the trajectory from normal to cancer cell is limited. Here we whole-genome sequenced 152 crypts from normal and neoplastic epithelial tissues from LS patients. In normal tissues the repertoire of mutational processes and mutation rates were similar to those found in wild type individuals. A morphologically normal colonic crypt with an increased mutation burden and mutational signatures consistent with MMR deficiency was identified, which may represent a very early stage of LS pathogenesis. Phylogenetic tress of tumour crypts indicated that the most recent ancestor cell of each tumour was already MMR deficient and had experienced multiple clonal evolution cycles. This study demonstrates the genomic stability of epithelial cells with heterozygous germline MMR gene mutations and highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.	Illumina NovaSeq 6000	161

Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___LYNCH___WGS

Exploring_the_landscape_of_somatic_mutations_in_normal_tissue_GI_LYNCH___WGS