• What is SRSF2?
  • SRSF2 in Myelodysplastic Syndromes
  • SRSF2 Mutations
  • Clinical Trials

SRSF2

Serine/arginine-rich splicing factor 2 (SRSF2) is a gene that codes for one of the several serine/arginine-rich splicing factors. SRSF2 is a member of the spliceosome and is involved in mRNA processing (Gene 2014). Spliceosome mutations are observed in MDS, chronic lymphocytic leukemia (CLL), AML, and chronic myelomonocytic leukemia (CMML), and these mutations can cause abnormal expression patterns of some genes involved in cancer pathogenesis (Chesnais et al. 2012).​

Related Pathways

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. SRSF2. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/srsf2/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

SRSF2 in Myelodysplastic Syndromes

SRSF2 mutations occur in 7.4% of MDS (COSMIC). SFSR2 mutations are most often observed in refractory cytopenia with multilineage dysplasia (RCMD) and refractory anemia with excess blasts (RAEB), two subtypes of high risk MDS (Cazzola, Della Porta, and Malcovati 2013). SRSF2 mutations are also common in patients with CMML, where they often co-occur with TET2 mutations (Cazzola, Della Porta, and Malcovati 2013). The role of SRSF2 mutations in MDS is not yet well understood (Visconte et al. 2012​). As in SF3B1, there is a mutational hotspot in SRSF2, involving an amino acid change at P95, found in the vast majority of all cases of SRSF2 mutations in MDS.

SRSF2 mutations have been associated with less favorable overall survival and a higher likelihood of transformation to AML (Damm et al. 2012; NCCN 2014; Thol et al. 2012).​

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. SRSF2 in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/srsf2/ (Updated September 23).

Last Updated: September 23, 2014

SRSF2 Mutations in Myelodysplastic Syndromes

Properties
Location of mutations SRSF2 gene on 17q25.1
Frequency of SRSF2 mutations in MDS 7.4% (COSMIC)
Implications for Targeted Therapeutics
Response to bromodomain inhibitors, DOT1L inhibitors, or other targeted epigenetic therapies Unknown at this timea
Response to spliceosome-targeting therapies Unknown at this timeb
Response to Ras-targeting therapies Unknown at this timec

The most frequently mutated position of SRSF2 is P95 (87.9%; COSMIC). SRSF2 mutations have been associated with less favorable overall survival and a higher likelihood of transformation to AML (Damm et al. 2012; NCCN 2014; Thol et al. 2012).

a Bromodomain (BRD2, BRD3, BRD4, and BRDt) inhibitors and DOT1L inhibitors are in phase I studies in hematologic malignancies (Abdel-Wahab and Levine 2013). In addition, several other epigenetic targeted therapies, targeting IDH1/IDH2, EZH2, LSD1, or UTX/JMJD3, are in development (Abdel-Wahab and Levine 2013).

b Drugs targeting the spliceosome are in development; these drugs alter gene expression or affect alternative splicing in ways that inhibit cancer progression (Bonnal, Vigevani, and Valcarcel 2012).

c Efforts to develop Ras-targeting therapies are in progress and are hoped to be useful in hematologic malignancies (Ward, Braun, and Shannon 2012).

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. SRSF2 Mutations in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/srsf2/328/ (Updated September 23).

Last Updated: September 23, 2014

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