KNSTRN

Gene Summary

Gene:KNSTRN; kinetochore localized astrin (SPAG5) binding protein
Aliases: SKAP, HSD11, C15orf23, TRAF4AF1
Location:15q15.1
Summary:-
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:small kinetochore-associated protein
Source:NCBIAccessed: 31 August, 2019

Cancer Overview

Lee CS et al, Nat Genet. 2014 found recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). In particular they found that mutations encoding p.Ser24Phe disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo.

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • DNA Mutational Analysis
  • Keratinocytes
  • SKAP protein, human
  • Polymerase Chain Reaction
  • Mutation
  • Point Mutation
  • Ultraviolet Rays
  • Single-Stranded Conformational Polymorphism
  • Tumor Suppressor Proteins
  • BUB1B
  • Skin Cancer
  • TP53
  • Dogs
  • Horses
  • Squamous Cell Carcinoma
  • Soft Tissue Sarcoma
  • Aneuploidy
  • NRAS
  • Leukaemia
  • Cultured Cells
  • Mice, Inbred NOD
  • Oral Cavity Cancer
  • p53 Protein
  • Oncogenes
  • MDM2
  • Immunohistochemistry
  • Neoplasm Proteins
  • Cancer Gene Expression Regulation
  • Carcinogenesis
  • Cell Cycle Proteins
  • Melanoma
  • Microtubule-Associated Proteins
  • Xanthomatosis
  • PTEN
  • Chromosome 15
  • BRCA2 Protein
  • Kinetochores
  • DNA Copy Number Variations
  • High-Throughput Nucleotide Sequencing
  • Species Specificity
Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (1)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Skin, Squamous Cell CarcinomaKNSTRN mutations in Cutaneous Squamous Cell Carcinoma
Lee CS et al (2014) reported recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous SCCs.
View Publications0

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: KNSTRN (cancer-related)

Wong K, van der Weyden L, Schott CR, et al.
Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma.
Nat Commun. 2019; 10(1):353 [PubMed] Free Access to Full Article Related Publications
Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.

Helbig D, Ihle MA, Pütz K, et al.
Oncogene and therapeutic target analyses in atypical fibroxanthomas and pleomorphic dermal sarcomas.
Oncotarget. 2016; 7(16):21763-74 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Until now, almost nothing is known about the tumorigenesis of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Our hypothesis is that AFX is the non-infiltrating precursor lesion of PDS.
MATERIALS AND METHODS: We performed the world-wide most comprehensive immunohistochemical and mutational analysis in well-defined AFX (n=5) and PDS (n=5).
RESULTS: In NGS-based mutation analyses of selected regions by a 17 hotspot gene panel of 102 amplicons we could detect TP53 mutations in all PDS as well as in the only analyzed AFX and PDS of the same patient. Besides, we detected mutations in the CDKN2A, HRAS, KNSTRN and PIK3CA genes.Performing immunohistochemistry for CTNNB1, KIT, CDK4, c-MYC, CTLA-4, CCND1, EGFR, EPCAM, ERBB2, IMP3, INI-1, MKI67, MDM2, MET, p40, TP53, PD-L1 and SOX2 overexpression of TP53, CCND1 and CDK4 was seen in AFX as well as in PDS. IMP3 was upregulated in 2 AFX (weak staining) and 4 PDS (strong staining).FISH analyses for the genes FGFR1, FGFR2 and FGFR3 revealed negative results in all tumors.
CONCLUSIONS: UV-induced TP53 mutations as well as CCND1/CDK4 changes seem to play essential roles in tumorigenesis of PDS. Furthermore, we found some more interesting mutated genes in other oncogene pathways (activating mutations of HRAS and PIK3CA). All AFX and PDS investigated immunohistochemically presented with similar oncogene expression profiles (TP53, CCND1, CDK4 overexpression) and the single case with an AFX and PDS showed complete identical TP53 and PIK3CA mutation profiles in both tumors. This reinforces our hypothesis that AFX is the non-infiltrating precursor lesion of PDS.

Lee JH, Kim MS, Yoo NJ, Lee SH
Absence of KNSTRN Mutation, a Cutaneous Squamous Carcinoma-Specific Mutation, in Other Solid Tumors and Leukemias.
Pathol Oncol Res. 2016; 22(1):227-8 [PubMed] Related Publications

Jaju PD, Nguyen CB, Mah AM, et al.
Mutations in the Kinetochore Gene KNSTRN in Basal Cell Carcinoma.
J Invest Dermatol. 2015; 135(12):3197-3200 [PubMed] Free Access to Full Article Related Publications


KNSTRN deemed an oncogene.
Cancer Discov. 2014; 4(11):1247 [PubMed] Related Publications

Lee CS, Bhaduri A, Mah A, et al.
Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma.
Nat Genet. 2014; 46(10):1060-2 [PubMed] Free Access to Full Article Related Publications
Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.

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Cite this page: Cotterill SJ. KNSTRN, Cancer Genetics Web: http://www.cancer-genetics.org/KNSTRN.htm Accessed:

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