Co-occurrence of Myeloproliferative Neoplasms and Solid Tumors Is Attributed to a Synergism Between Cytoreductive Therapy and the Common TERT Polymorphism rs2736100.
BACKGROUND
The germline telomerase reverse transcriptase (TERT) rs2736100_C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN).


METHODS
LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100_C and Janus kinase 2 (JAK2) rs12343867_C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals.


RESULTS
TERT rs2736100_C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7%±2.8% vs. 48.8%±3.5%, P < 0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4%) to die from solid tumors compared with TERT AC/AA individuals (5.3%; P = 0.004). TERT rs2736100_C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03-9.26), P = 0.045].


CONCLUSIONS
TERT rs2736100_C polymorphism predisposes to the development of BCR-ABL1-negative MPN with the co-occurrence of solid tumors, especially with the usage of cytoreductive treatment.


CONCLUSIONS
The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients.
Semmelweis University, Doctoral School, Budapest, Hungary. Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
Tunde
T
Krahling
Semmelweis University, Doctoral School, Budapest, Hungary. Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
Katalin
K
Balassa
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
Katalin Piroska
KP
Kiss
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
Andras
A
Bors
Department of Haematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest, Hungary.
Arpad
A
Batai
Department of Haematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest, Hungary.
Gabriella
G
Halm
Department of Haematology, Kaposi Mor Hospital, Kaposvar, Hungary.
Miklos
M
Egyed
Department of Haematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest, Hungary.
Sandor
S
Fekete
Department of Haematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest, Hungary.
Peter
P
Remenyi
Department of Haematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest, Hungary. 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Tamas
T
Masszi
Institute of Pathophysiology, Semmelweis University, Budapest, Hungary.
Attila
A
Tordai
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary. andrikovics.hajnalka@ovsz.hu.
Hajnalka
H
Andrikovics
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D065426:Cytoreduction Surgical Procedures / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015994:Incidence; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C509186:TERT protein, human; D019098:Telomerase