Ann Lab Med.  2015 Jan;35(1):118-122. 10.3343/alm.2015.35.1.118.

Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

• Choi HW
• Kim HR
• Baek HJ
• Kook H
• Cho D
• Shin JH
• Suh SP
• Ryang DW
• Shin MG

• KMID: 2363158
• DOI: http://doi.org/10.3343/alm.2015.35.1.118

Abstract

BACKGROUND
Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML.
METHODS
Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients.
RESULTS
Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients.
CONCLUSIONS
Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.

Keyword

SETBP1; SF3B1; U2AF1; SRSF2; AML; Childhood

MeSH Terms

Adolescent
Carrier Proteins/*genetics
Child
Child, Preschool
Cohort Studies
Cytogenetic Analysis
DNA Mutational Analysis
Female
Gene Frequency
Genotype
Humans
Infant
Leukemia, Myeloid, Acute/*genetics/pathology
Male
Nuclear Proteins/*genetics
Phosphoproteins/*genetics
Polymorphism, Single Nucleotide
RNA Splicing
Ribonucleoprotein, U2 Small Nuclear/*genetics
Ribonucleoproteins/*genetics
Carrier Proteins
Nuclear Proteins
Phosphoproteins
Ribonucleoprotein, U2 Small Nuclear
Ribonucleoproteins

Figure

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  Fig. 1 Electropherograms of the patient with a synonymous SETBP1 gene alteration. The synonymous alteration of c.2903C>T evident at diagnosis (A) disappeared on day 30 of the second induction of chemotherapy (B) and reappeared during consolidation therapy (C).

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