Characterization of New <i>ATM</i> Deletion Associated with Hereditary Breast Cancer

• Main Authors: Sandra Parenti, Claudio Rabacchi, Marco Marino, Elena Tenedini, Lucia Artuso, Sara Castellano, Chiara Carretta, Selene Mallia, Laura Cortesi, Angela Toss, Elena Barbieri, Rossella Manfredini, Mario Luppi, Tommaso Trenti, Enrico Tagliafico
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Genes
• Subjects: next-generation sequencing; breast cancer; <i>ATM</i>; homologous recombination repair; hereditary cancer syndromes; clinical genomics
• Online Access: https://www.mdpi.com/2073-4425/12/2/136

Next-generation sequencing (NGS)-based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. <i>ATM</i> germ-line heterozygosity has been described to increase tumor susceptibility. In particular, families carrying heterozygous germ-line variants of <i>ATM</i> gene have a 5- to 9-fold risk of developing breast cancer. Recent studies identified <i>ATM</i> as the second most mutated gene after <i>CHEK2</i> in BRCA-negative patients. Nowadays, more than 170 missense variants and several truncating mutations have been identified in <i>ATM</i> gene. Here, we present the molecular characterization of a new <i>ATM</i> deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics’ Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed us to identify a new inactivating deletion of exons 19–27 of <i>ATM</i> gene. The deletion was characterized both at the DNA and RNA level.