Supplementary Figure S1 from PIGA Mutations and Glycosylphosphatidylinositol Anchor Dysregulation in Polyposis-Associated Duodenal Tumorigenesis

Meuser, Elena; Chang, Kyle; Walters, Angharad; Hurley, Joanna J.; West, Hannah D.; Perry, Iain; Mort, Matthew; Reyes-Uribe, Laura; Truscott, Rebekah; Jones, Nicholas; Lawrence, Rachel; Jenkins, Gareth; Giles, Peter; Dolwani, Sunil; Al-Sarireh, Bilal; Hawkes, Neil; Short, Emma; Williams, Geraint T.; Taggart, Melissa W.; Luetchford, Kim; Lynch, Patrick M.; Terlouw, Diantha; Nielsen, Maartje; Walton, Sarah-Jane; Latchford, Andrew; Clark, Susan K.; Sampson, Julian R.; Vilar, Eduardo; Thomas, Laura E.

doi:10.1158/1541-7786.25964955.v1

Supplementary Figure S1 from PIGA Mutations and Glycosylphosphatidylinositol Anchor Dysregulation in Polyposis-Associated Duodenal Tumorigenesis

journal contribution

posted on 2024-06-04, 07:41 authored by Elena Meuser, Kyle Chang, Angharad Walters, Joanna J. Hurley, Hannah D. West, Iain Perry, Matthew Mort, Laura Reyes-Uribe, Rebekah Truscott, Nicholas Jones, Rachel Lawrence, Gareth Jenkins, Peter Giles, Sunil Dolwani, Bilal Al-Sarireh, Neil Hawkes, Emma Short, Geraint T. Williams, Melissa W. Taggart, Kim Luetchford, Patrick M. Lynch, Diantha Terlouw, Maartje Nielsen, Sarah-Jane Walton, Andrew Latchford, Susan K. Clark, Julian R. Sampson, Eduardo Vilar, Laura E. Thomas

Whole transcriptome sequencing quality control and read distribution for data sets from Cardiff and MD Anderson. A. Sequencing quality assessment, batch aggregates are shown. B. Read distribution across the genome per batch demonstrating that over 80% of reads mapped to known exons. CDS=Coding sequence; MDA=MD Anderson Cancer Center data; TES=Transcription end site; TSS=Transcription start site; UTR=Untranslated region.

Funding

Health and Care Research Wales (HCRW)

National Institutes of Health (NIH)

History

ARTICLE ABSTRACT

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA. PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.