The human tumour-associated epithelial mucins are coded by an expressed hypervariable gene locus PUM

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• A single autosomal gene locus, PUM, encodes mucin-type glycoproteins identified initially in human urine.
• These glycoproteins are also present in epithelial tissues, bodily fluids like milk, and epithelial-origin tumors.
• Mucin-type glycoproteins are highly immunogenic, prompting research into epithelial-specific or tumor-associated antigens.

Purpose of the Study:

• To investigate the expression of PUM-coded mucins in normal and malignant cells.
• To characterize the PUM locus and its expressed gene product.
• To confirm the relationship between DNA polymorphism and protein polymorphism.

Main Methods:

• Isolation of complementary DNA (cDNA) coding for mammary mucin.
• Analysis of PUM locus using isolated cDNA.
• SDS-gel electrophoresis to separate glycoproteins.
• Immunohistology to assess antibody specificity.

Main Results:

• The PUM locus is a hypervariable minisatellite region of human DNA.
• This minisatellite region is unique as it is transcribed and translated into glycoproteins.
• The polymorphism within the PUM minisatellite DNA is also detectable in the expressed gene product (mucin-type glycoproteins).
• Numerous antibodies binding PUM-coded mucins exhibit tumor specificity.

Conclusions:

• The PUM locus represents a novel, transcribed, and translated hypervariable minisatellite region.
• The demonstrated polymorphism in both DNA and protein products has implications for cancer research.
• PUM-coded mucins and their associated antibodies are valuable tools for cancer diagnosis and potentially therapy.