Identification of <b><i>CHEK2</i></b> Germline Mutations in <b><i>BRCA1/2-</i></b> and <b><i>PALB2</i></b>-Negative Breast and Ovarian Cancer Patients

Abstract

<b><i>Introduction:</i></b> The <i>CHEK2</i> gene is known to be an important signal transducer involved in DNA repair, apoptosis, or cell cycle arrest in response to DNA damage. The mutations in this gene have been associated with a wide range of cancers, both sporadic and hereditary. Germline <i>CHEK2</i> mutations are linked to an increased risk of breast cancer. Therefore, the aim of this study was to identify the prevalence of <i>CHEK2</i> variants in <i>BRCA1/2-</i> and <i>PALB2</i>-negative early-onset patients with breast cancer and/or ovarian cancer in a Turkish population for the first time. <b><i>Methods:</i></b> The study included 95 patients with <i>BRCA1/2-</i> and <i>PALB2-</i>negative early-onset breast cancer and/or ovarian cancer and also 60 unaffected women. All the intron/exon boundaries and coding exons of <i>CHEK2</i> were subjected to mutational analysis by heteroduplex analysis and DNA sequencing. <b><i>Results:</i></b> A total of 16 <i>CHEK2</i> variants were found in breast cancer patients within the Turkish population. <i>CHEK2</i> c.1100delC mutation most frequently studied in the <i>CHEK2</i> gene was not detected in our study. The prevalence of variants of uncertain significance in <i>CHEK2</i> was found to be 7.3% (<i>n</i> = 7) in <i>BRCA1/2</i> and <i>PALB2</i> mutation-negative Turkish patients with early-onset breast and/or ovarian cancer. <b><i>Conclusion:</i></b> The present study may shed light on alternative variations that could be significant for understanding the prevalence and clinical suitability of the <i>CHEK2</i> gene.