ATM Gene Deletion: A Rare Etiology for Hereditary Cancers

Ataxia Telangiectasia Mutated (ATM) gene helps to repair DNA damage and that increased cancer risks are associated with having a mutation in an ATM gene. ATM gene is newer compared to other known hereditary cancer genes. We present a rare care of 66-year-old female with extensive personal and family history of breast and pancreatic cancer had negative imaging surveillance until recent systemic imaging showed new pancreatic head 2.5x2.5 cm mass. Endoscopic ultrasound confirmed invasion of superior mesenteric vein with near confluence. No regional adenopathy was seen. She was felt to be borderline resectable and neoadjuavant chemotherapy was planned. She had a personal history of right breast cancer diagnosed in 1998 status post lumpectomy and axillary lymph node dissection and adjuvant chemotherapy with CMF regimen x 5 cycles and radiation therapy and endocrine therapy with tamoxifen for 5 years. In 2011 she was also diagnosed with rectal well to moderately differentiated adenocarcinoma status post abdominoperitoneal resection on 3/15/2011, 36 lymph nodes were negative, but the surgical circumferential radial margin was positive. She underwent adjuvant radiation therapy with total dose of 45 Gy. There was recurrence in vaginal and bladder wall adenocarcinoma in 2014 for which patient underwent an anterior exenteration. Pathology felt this was endocervical origin of malignancy and patient received megace therapy for 3 years based on hormone receptor positive status. For new diagnosis of pancreatic adenocarcinoma, she was started on Gemcitabine and Abraxane chemotherapy. Given extensive personal and family history of malignancy, she was referred to genetic counsellor. Hereditary cancers panel at invitae laboratory was positive for a heterozygous pathological variant in the ATM gene deletion (exons 62-63). ATM gene is associated with an increased risk for autosomal dominant breast, pancreatic and prostate cancer. Close relatives (children, siblings, and each parent) have up to a 50% chance of being a carrier of this variant. It is essential for treating physicians to educate patients and family members on the risk for subsequent malignancies