Increased copy number at 3p14 in breast cancer

Area of Science:

• Oncology
• Human Genetics
• Molecular Biology

Background:

• Genetic studies suggest a tumor suppressor gene on chromosome 3p is involved in breast cancer.
• LRIG1 at 3p14 is a candidate tumor suppressor, encoding a protein that regulates ERBB receptor tyrosine kinases.
• LRIG1 is expressed in various tissues, including breast tissue.

Purpose of the Study:

• To investigate the pathogenic significance of chromosome band 3p14 in breast cancer.
• To analyze the LRIG1 gene, mRNA, and protein in breast tumors.
• To determine the association between LRIG1 alterations and breast cancer malignancy.

Main Methods:

• Fluorescence in situ hybridization (FISH) for LRIG1 gene copy number.
• Quantitative reverse transcription PCR (RT-PCR) for LRIG1 mRNA expression.
• Western blot analysis for LRIG1 protein levels.
• Analysis of two breast tumor series (n=28 and n=9) with matched non-neoplastic tissues.

Main Results:

• Increased LRIG1 gene copy number was found in 39% (11/28) of tumors; only one tumor showed deletion.
• Increased LRIG1 copy number correlated with elevated LRIG1 mRNA levels in 2/3 tumors.
• Elevated LRIG1 protein levels were observed in all tested tumors (4/4) with increased copy number compared to matched controls.

Conclusions:

• The role of LRIG1 as an ERBB receptor inhibitor raises questions about the significance of its increased copy number in breast cancer.
• A novel breast cancer-associated gene may be located within the amplicon at 3p14.3, encompassing the LRIG1 locus.