Alternative titles; symbols
HGNC Approved Gene Symbol: LZTS1
Cytogenetic location: 8p21.3 Genomic coordinates (GRCh38) : 8:20,246,165-20,303,963 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8p21.3 | Esophageal squamous cell carcinoma, somatic | 133239 | 3 |
Ishii et al. (1999) positionally cloned and characterized the FEZ1/LZTS1 (leucine zipper, putative tumor suppressor-1) gene at 8p22, a region that is lost in many tumors, including prostate, breast, head and neck, esophageal, and urinary bladder carcinomas. The predicted FEZ1 protein contained a leucine zipper region with similarity to the DNA-binding domain of the cAMP-responsive activating transcription factor-5 (606398). Northern blot analysis revealed that FEZ2 is expressed almost ubiquitously in normal tissues, although expression is most abundant in testes. FEZ1 expression was undetectable in more than 60% of epithelial tumors, but FEZ1 mutations were found in primary esophageal cancers and in a prostate cancer cell line. Transcript analysis from several FEZ1-expressing tumors revealed truncated mRNAs, including a frameshift. Alteration and inactivation of the FEZ1 gene may play a role in various human tumors.
Ishii et al. (2001) showed that introduction of FEZ1/LZTS1 into FEZ1/LZTS1-negative cancer cells resulted in suppression of tumorigenicity and reduced cell growth with accumulation of cells at late S-G2/M stage of the cell cycle. Their data showed that FEZ1/LZTS1 inhibits cancer cell growth through regulation of mitosis, and that its alterations result in abnormal cell growth.
Ishii et al. (1999) analyzed the nucleotide sequence of the FEZ1 gene open reading frame in 194 cancers, including 72 primary esophageal cancers. They found a point mutation in 2 primary esophageal cancers and in a prostate cancer cell line.
The chromosome 8p23-p22 region has been identified as a potential site for genes associated with prostate cancer (176807). The LZTS1 gene, which maps to this region, was identified as a potential tumor suppressor based on loss of heterozygosity (LOH) studies using primary esophageal tumors. Furthermore, sequence analysis of mRNA from various tumors showed multiple mutations and aberrant mRNA transcripts. Hawkins et al. (2002) performed sequence analysis of LZTS1 in a panel of sporadic and hereditary prostate cancer cases and unaffected controls. They found 4 SNPs that were statistically significant for association with prostate cancer.
In a primary esophageal tumor (see 133239), Ishii et al. (1999) found an alteration of TCC to CCC at codon 29 of the LZTS1 gene, resulting in the substitution of ser29 with pro29 (S29P). Ser29 is a predicted cAMP-dependent kinase phosphorylation site. The sequences from normal DNA of the same patient showed no alterations. A loss of heterozygosity (LOH) study indicated that this and a second patient with a mutation in the LZTS1 gene had allelic loss of the normal allele.
Ishii et al. (1999) demonstrated a somatic mutation in esophageal squamous cell carcinoma (see 133239): AAG (lys) to GAG (glu) at codon 119 of the LZTS1 gene (K119E). An LOH study indicated that the normal allele had been lost by deletion.
Hawkins, G. A., Mychaleckyj, J. C., Zheng, S. L., Faith, D. A., Kelly, B., Isaacs, S. D., Wiley, K. E., Chang, B.-L., Ewing, C. M., Bujnovszky, P., Bleecker, E. R., Walsh, P. C., Meyers, D. A., Isaacs, W. B., Xu, J. Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk. Cancer Genet. Cytogenet. 137: 1-7, 2002. [PubMed: 12377406] [Full Text: https://doi.org/10.1016/s0165-4608(02)00549-6]
Ishii, H., Baffa, R., Numata, S.-I., Murakumo, Y., Rattan, S., Inoue, H., Mori, M., Fidanza, V., Alder, H., Croce, C. M. The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors. Proc. Nat. Acad. Sci. 96: 3928-3933, 1999. [PubMed: 10097140] [Full Text: https://doi.org/10.1073/pnas.96.7.3928]
Ishii, H., Vecchione, A., Murakumo, Y., Baldassarre, G., Numata, S., Trapasso, F., Alder, H., Baffa, R., Croce, C. M. FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proc. Nat. Acad. Sci. 98: 10374-10379, 2001. [PubMed: 11504921] [Full Text: https://doi.org/10.1073/pnas.181222898]