Alteration of SF3B1 and SRSF2 Genes in Myelodysplastic Syndromes Patients in Upper Northern Thailand

Autor: Kanokkan Bumroongkit, Sikrai Laowatthanapong, Phuttirak Yimpak, Witoon Tasuya, Adisak Tantiworawit, Thanawat Rattanathammethee, Sirinda Angsuchawan
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
DNA Mutational Analysis
Gene mutation
Hemoglobin levels
Gastroenterology
law.invention
03 medical and health sciences
symbols.namesake
0302 clinical medicine
law
Internal medicine
Biomarkers
Tumor
medicine
Humans
Gene
Polymerase chain reaction
Aged
SRSF2 gene mutation
Aged
80 and over
Sanger sequencing
Serine-Arginine Splicing Factors
business.industry
SF3B1 gene mutation
Myelodysplastic syndromes
splicing machinery gene
Myeloid leukemia
General Medicine
Middle Aged
Phosphoproteins
Prognosis
Thailand
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Myelodysplastic Syndromes
030220 oncology & carcinogenesis
Mutation
symbols
Female
RNA Splicing Factors
Bone marrow
business
Myelodysplastic syndrome
Follow-Up Studies
Research Article
Zdroj: Asian Pacific Journal of Cancer Prevention : APJCP
ISSN: 2476-762X
DOI: 10.31557/apjcp.2019.20.4.1215
Popis: Background: The frequency and pattern of mutation in SF3B1 and SRSF2 RNA splicing machinery genes were found to vary among myelodysplastic syndrome (MDS) patients in different populations. There have been less reports of incidence of these gene mutations in Thailand especially in upper northern Thailand. This study therefore had aims to investigate the frequency and pattern of mutation in mutational hotspot of SF3B1 and SRSF2 genes among MDS patients in upper northern Thailand and to investigate the clinical features associated with the mutations. Methods: Fifty-five MDS patients who underwent treatment at Maharaj Nakorn Chiang Mai Hospital participated in this study. The detection of SF3B1 and SRSF2 hotspot mutations was carried out using polymerase chain reaction followed by Sanger sequencing. In addition, clinical features of individual patients with these gene mutations were also investigated. Results: SF3B1 mutations (SF3B1mut) were found in 9 patients (16.4%) including E622D (1/9), R625C (1/9), H662Q (1/9), K700E (5/9), and Q699H co-mutation with K700E (1/9). SRSF2 mutations (SRSF2mut) were found in 4 patients (7.3%) which included P95H (3/4) and P95L (1/4). The SF3B1mut was associated with lower hemoglobin levels (p = 0.023) and higher platelet counts (p = 0.047) when compared with MDS patients without SF3B1mut, while SRSF2mut tended to occur in patients with a higher percentage of bone marrow blasts (p = 0.074). Conclusion: The findings confirmed the difference in frequency of SF3B1 and SRSF2 mutations among different populations. Specifically, we found a co-mutation of Q699H and K700E that has not been previously reported in MDS patients in the COSMIC database. It was also found that SF3B1mut was strongly associated with low hemoglobin level, and high platelet counts whereas SRSF2mut was mostly clustered in MDS with excess blasts subsequently increasing the probability of progression to acute myeloid leukemia.
Databáze: OpenAIRE
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