Premium
Germline mutations in Protection of Telomeres 1 in two families with Hodgkin lymphoma
Author(s) -
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
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15203
Subject(s) - telomere , biology , germline , mutant , genetics , lymphoma , mutation , gene , germline mutation , telomere binding protein , microbiology and biotechnology , shelterin , cancer research , immunology , dna binding protein , transcription factor
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 POT 1 (D224N and Y36H), both in a highly conserved region of the gene. POT 1 D224N mutant did not bind to a single‐stranded telomere oligonucleotide in vitro suggesting the mutation perturbs POT 1's ability to bind to the telomeric G‐rich overhang. Human HT 1080 cells expressing POT 1 D224N and lymphoblastoid cells carrying Y36H both showed increased telomere length and fragility in comparison to wild type cells. This strongly suggests that mutant POT 1 causes chromosome instability and may play a role in lymphomagenesis in these families.