title: Genetic variants of mucins: unexplored conundrum.
abstract: Alternative gene splicing, occurring ubiquitously in multicellular organisms can produce several protein isoforms with putatively different functions. The enormously extended genomic structure of mucin genes characterized by the presence of multiple exons encoding various domains may result in functionally diverse repertoire of mucin proteins due to alternative splicing. Splice variants (Svs) and mutations in mucin genes have been observed in various cancers and shown to participate in cancer progression and metastasis. Although several mucin Svs have been identified, their potential functions remain largely unexplored with the exception of the Svs of MUC1 and MUC4. A few studies have examined the expression of MUC1 and MUC4 Svs in cancer and indicated their potential involvement in promoting cancer cell proliferation, invasion, migration, angiogenesis and inflammation. Herein we review the current understanding of mucin Svs in cancer and inflammation and discuss the potential impact of splicing in generating a functionally diverse repertoire of mucin gene products. We also performed mutational analysis of mucin genes across five major cancer types in International Cancer Genome Consortium database and found unequal mutational rates across the panel of cancer-associated mucins. Although the functional role of mucins in the pathobiology of various malignancies and their utility as diagnostic and therapeutic targets remain undisputed, these attributes need to be reevaluated in light of the potentially unique functions of disease-specific genetic variants of mucins. Thus, the expressional and functional characterization of the genetic variants of mucins may provide avenues to fully exploit their potential as novel biomarkers and therapeutic targets.
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Eric
authors.initials: E
authors.lastname: Cruz
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Suhasini
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Asish
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Rahat
authors.initials: R
authors.lastname: Jahan
authors.affiliation: Department of Biochemistry and Molecular Biology.|Eppley Institute for Research in Cancer and Allied Diseases.|Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
authors.affiliation: Department of Biochemistry and Molecular Biology.|Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics*
chemical_list: D009077:Mucins; D020033:Protein Isoforms