Differential expression of CHL1 Gene in early-onset breast cancer patients and their parents

Introduction: The purpose of this study was to determine a correlation between less expression of CHL1 or deletions close to the CHL1 gene, which might be associated with an elevated risk for breast cancer at a young age.

Methods: 50 research subjects recruited to the Washington University/Siteman Cancer Center Young Women's Breast Cancer Program (YWBCP) were selected for study. CGH analyses were undertaken using the NimbleGen 2.1 million oligonucleotide array. The number of copies of the entire genome was compared between the proband and each of her parents to identify potential deletion or amplification in her relative to both parents.

Results: One proband showed a deletion in the region of interest not present in her parents. She showed an 11.56 bp deletion 5' of the CHL1 gene. Conventional PCR confirmed a deletion of an ˜ 3 kb region of a known CNV with a reported frequency of ˜3%. Testing an additional 858 young women breast cancer cases (YWBC), a frequency of the deletion in 5.9% of YWBC cases was revealed. 5.3% of the cancer free control cases (CFC) showed the deletion. In previous work on copy number variants in schizophrenia, 3.2% had this deletion. Our YWBC and CFC combined with the schizophrenia cohort did not show an association between the deletion and an elevated risk for early onset breast cancer (p-value = 0.1329).

Conclusions: Patients with early-onset breast cancer presumably harbor copy number changes not present in the genomes of their parents and as such may be causally associated with their disease.