Germline mutations in Protection of Telomeres 1 in two families with Hodgkin lymphoma. (25th April 2018)

• Record Type: Journal Article
• Authors: McMaster, Mary L.; Sun, Chongkui; Landi, Maria T.; Savage, Sharon A.; Rotunno, Melissa ; Yang, Xiaohong R.; Jones, Kristine; Vogt, Aurélie; Hutchinson, Amy; Zhu, Bin; Wang, Mingyi; Hicks, Belynda; Thirunavukarason, Anand; Stewart, Douglas R.; Koutros, Stella; Goldstein, Alisa M.; Chanock, Stephen J.; Caporaso, Neil E.; Tucker, Margaret A.; Goldin, Lynn R.; Liu, Yie
• Is Part Of: British journal of haematology. Volume 181:Number 3(2018)
• Page Start: 372
• Page End: 377
• Publication Date: 2018-04-25
• Subjects: Hodgkin lymphoma -- genetic analysis -- genomic instability -- telomere -- POT1; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.15203
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: In a previous whole exome sequencing of patients from 41 families with Hodgkin lymphoma, we identified two families with distinct heterozygous rare coding variants in POT1 (D224N and Y36H), both in a highly conserved region of the gene. POT1 D224N mutant did not bind to a single‐stranded telomere oligonucleotide in vitro suggesting the mutation perturbs POT1's ability to bind to the telomeric G‐rich overhang. Human HT1080 cells expressing POT1 D224N and lymphoblastoid cells carrying Y36H both showed increased telomere length and fragility in comparison to wild type cells. This strongly suggests that mutant POT1 causes chromosome instability and may play a role in lymphomagenesis in these families.