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A cell cycle regulator potentially involved in genesis of many tumor types
A Kamb1, N A Gruis, J Weaver-Feldhaus
1Myriad Genetics, Inc., Salt Lake City, UT 84108.
Abstract:
A putative tumor suppressor locus on the short arm of human chromosome 9 has been localized to a region of less than 40 kilobases by means of homozygous deletions in melanoma cell lines. This region contained a gene, Multiple Tumor Suppressor 1 (MTS1), that encodes a previously identified inhibitor (p16) of cyclin-dependent kinase 4. MTS1 was homozygously deleted at high frequency in cell lines derived from tumors of lung, breast, brain, bone, skin, bladder, kidney, ovary, and lymphocyte. Melanoma cell lines that carried at least one copy of MTS1 frequently carried nonsense, missense, or frameshift mutations in the gene. These findings suggest that MTS1 mutations are involved in tumor formation in a wide range of tissues.
Insights
The Multiple Tumor Suppressor 1 (MTS1) gene, a key tumor suppressor, is frequently deleted or mutated in many cancers. These genetic alterations in MTS1 are implicated in the development of diverse tumor types.
Area of Science:
- Oncology
- Human Genetics
- Molecular Biology
Background:
- A specific region on chromosome 9 short arm is implicated as a tumor suppressor locus.
- Homozygous deletions in melanoma cell lines narrowed this locus to under 40 kilobases.
Purpose of the Study:
- To identify and characterize the gene within the defined tumor suppressor locus.
- To investigate the role of this gene in various cancer types.
Main Methods:
- Fine mapping of homozygous deletions in melanoma cell lines.
- Gene sequencing to identify mutations.
- Analysis of gene frequency in diverse tumor cell lines.
Main Results:
- The tumor suppressor gene Multiple Tumor Suppressor 1 (MTS1), encoding p16, was identified in the critical region.
- MTS1 was homozygously deleted in a high frequency of lung, breast, brain, bone, skin, bladder, kidney, ovary, and lymphocyte tumor cell lines.
- Melanoma cell lines with MTS1 often harbored nonsense, missense, or frameshift mutations.
Conclusions:
- MTS1 functions as a critical tumor suppressor.
- Mutations and deletions in MTS1 are prevalent across a broad spectrum of human cancers.
- MTS1 alterations are significant contributors to tumorigenesis in multiple tissues.