Cancer treatments, including chemotherapy and radiotherapy, give a growth advantage to cells with particular genetic changes in healthy tissue, new research finds.

Highlights

• Integrin alpha 3 (ITGA3) protein expression was detected in approximately 85% of breast cancer specimens by immunohistochemistry.

• ITGA3 expression was significantly higher in human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor(HR)-positive/HER2-negative breast cancer than in triple-negative breast cancer (TNBC).

• High ITGA3 protein expression was associated with shorter 5-year recurrence-free survival.

• ITGA3 alterations in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort were associated with worse relapse-free and overall survival.

• Integrin α3β1 represents a potential prognostic biomarker and therapeutic target warranting prospective validation.

Pediatric chemotherapy can leave lasting genetic scars on the healthy tissues of children treated for cancer, researchers report, potentially helping explain some of the long-term health problems childhood cancer survivors face decades later in life. Chemotherapy drugs such as cisplatin and carboplatin can kill cancer cells by damaging DNA. Yet, despite their benefits, they can also leave characteristic mutations in healthy tissues, particularly blood. However, the extent to which treatment produces mutations across different tissues in the same person remains unclear. This question is especially important for children, who may carry the consequences of chemotherapy-related mutations for decades and potentially face an increased risk of future cancers. Anna Wenger and colleagues used the highly sensitive duplex sequencing technology, NanoSeq, to detect mutations originating from individual DNA molecules in non-cancerous tissues from pediatric cancer patients. They also used targeted, gene-focused sequencing to examine the types and potential future consequences of chemotherapy-induced mutations. Wenger et al. found that non-cancerous liver tissue in children exposed to platinum-based chemotherapy accumulated mutation levels comparable to those of adult livers. The authors also identified a distinctive mutational signature found in cisplatin-exposed liver tissue, both healthy and cancerous, but not in other organs or cancer types, providing evidence that platinum treatment can leave specific patterns of lasting genetic damage in healthy tissue. “Wenger et al.’s study adds to the evidence that platinum agents can induce a high number of mutations in the normal [non-cancerous] tissues of children treated for liver cancer, for whom this type of chemotherapy is important for long-term survival,” write Sanjeev Vasudevan and D. Williams Parsons in a related Perspective. “Studies that follow treated children into late adulthood will enable earlier recognition of liver dysfunction and earlier interventions for any new cancers that arise in this population.”