SF3B1 mutation is a poor prognostic indicator in luminal B and progesterone receptor-negative breast cancer patients

Abstract

The purpose of this study was to explore the relationship between SF3B1 mutations and the prognoses of patients with breast cancer. Clinical and SF3B1 mutation data from The Cancer Genome Atlas were analyzed. SF3B1 mutations were evaluated as prognostic factors in all breast cancer patients and specific subgroups through Cox regression and Kaplan-Meier analyses. We also investigated the relationship between traditional parameters and SF3B1 mutations. Receiver operating characteristics curves were used to analyze common risk factors for their sensitivity and specificity in predicting SF3B1 mutations. SF3B1 mutations were a poor prognostic factor in luminal B and progesterone receptor (PR)-negative breast cancer (P < 0.01). Age at diagnosis and estrogen receptor (ER) status were associated with SF3B1 mutations in all breast cancers (P < 0.01) and in luminal B and PR-negative subgroups (P < 0.01). The age at diagnosis and ER status combined had a higher sensitivity and specificity for predicting SF3B1 mutations than each factor alone. SF3B1 mutations are a poor prognostic factor in luminal B and PR-negative breast cancer patients. These mutations are significantly associated with age at diagnosis and ER status. SF3B1 mutations may therefore be a novel therapeutic target for breast cancer patients.

Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation

“…Knockin of mutant SF3B1 alters the transcriptome of breast epithelial cells. SF3B1 is recurrently mutated in 2% of breast cancers and associates with poor prognosis in subgroups of patients, but the functional role of the mutation in this cellular context has been unexplored (13,14). We therefore first aimed to characterize the isolated consequences of SF3B1 mutations in untransformed human breast epithelial cells.…”

Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns

“…I n various cancers, mutations in the splicing factor SF3B1 have been associated with characteristic alterations in splicing. In particular, recurrent somatic mutations in SF3B1 have been linked to various diseases, including chronic lymphocytic leukemia (CLL) [1][2][3][4] , uveal melanoma [5][6][7] , breast cancer [8][9][10] , and myelodysplastic syndromes 11,12 . SF3B1 is a core component of the U2 snRNP of the spliceosome and associates with the U2 snRNA and branch point adenosine of the pre-mRNA [13][14][15] .…”

Inhibition of Splicing Factor 3b Subunit 1 (SF3B1) Reduced Cell Proliferation, Induced Apoptosis and Resulted in Cell Cycle Arrest by Regulating Homeobox A10 (HOXA10) Splicing in AGS and MKN28 Human Gastric Cancer Cells

“…Small nuclear ribonucleoprotein (snRNP) complexes of protein and [17,18]. The spliceosome, splicing factor 3b subunit 1 (SF3B1), has previously been shown to play an important role in tumorigenesis and tumor progression [5,6]. However, the mechanism of SF3B1 in cancer and its downstream pathways remain unclear.…”

“…SF3B1 is located on chromosome 2q33.1 and results in alternative splicing events. Dysregulation of SF3B1 is associated with the progression of multiple malignant diseases, including breast cancer [5,6], head and neck cancer [7], and leukemia [8]. Importantly, snRNPs are attractive targets for anticancer treatment, and the agents targeting them has attracted considerable attention.…”