Oncology Companion Diagnostics
DescriptionWith an incidence of over 6,500 new cases per year only in the United States, Acute Lymphoblastic Leukaemia (ALL) is the most common cancer in children, representing one third of all childhood malignancies. Progressive intensification of multidrug chemotherapeutic regimens has improved outcomes for patients with ALL however up to 20% of patients treated with glucocorticoids relapse (reference therapy usually comprises the use of dexamethasone and/or prednisone). To date, there is no way to predict the clinical outcome of ALL patients when treated with conventional chemotherapy.
Polymorphisms in apoptosis-related genes, such as GSTM1 and TP53, have an impact on the outcome of childhood ALL. Presence of the combination of two polymorphisms (GSTM1 non-null genotype and p53Pro variant at codon 72 of TP53 gene) indicates an elevated probability of a worse outcome in childhood ALL patients. GSTM1 and TP53 would help to optimize cancer chemotherapeutic regimens.
Results are based on screening a total of 173 Caucasian children with ALL for detecting the presence of polymorphisms on gene copy number variants (CNV) CYP2D6, GSTT1, GSTM1, UGT2B17, and SULT1A1 genes and for single nucleotide polymorphisms (SNPs) at CYP2D6, SULT1A1, and TP53 genes. Results revealed that GSTM1 non-null genotype was associated with poor outcome. Additionally, there was a trend to reduced survival in patients with Pro variant at the TP53 Arg72Pro SNP. The combination of GSTM1 non-null and TP53 Pro/Pro or Pro/Arg genotype resulted in a highly significant reduction of survival.