Germline mutations in Protection of Telomeres 1 in two families with Hodgkin lymphoma

ML McMaster, C Sun, MT Landi… - British journal of …, 2018 - Wiley Online Library
ML McMaster, C Sun, MT Landi, SA Savage, M Rotunno, XR Yang, K Jones, A Vogt…
British journal of haematology, 2018Wiley Online Library
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 …
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.
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