Gene Expression Detection Assay for Cancer Clinical Use

Narrandes, Shavira; Xu, Wayne

Afirma®, a microarray assay developed by Veracyte Corporation (South San Francisco, California), is a gene expression classifier that measures the expression of 167 gene transcripts. It classifies aspirated material from thyroid nodules as either benign or suspicious. 30 MammaPrint is a 70-gene signature derived from 5000 expressed genes using a DNA microarray assay to predict the distant disease-free survival and overall survival in lymph-node negative patients. It has also been shown to have significant prognostic results in lymph-node positive tumors. Being cost-effective and shown to improve quality-adjusted survival, it identifies patients in the "low-risk" group with a >90% chance of being disease-free for a minimum of 5 years, allowing them to refrain from unnecessary adjuvant chemotherapy. 31 , 32 DNA microarrays have been used to determine the differences between the subtypes of lung squamous cell carcinomas (SCC) and stratify the patients for accurate prognoses and targeted research. One study used 382 SCC patients from five published cohorts of DNA microarrays to detect the subtypes and the collection and assay of 56 SCC patients for validation. Four independent subtypes were identified and statistics and bioinformatics were used to determine subtype survival outcome, clinical covariates, and biological processes. 33 DNA microarrays have also been employed to evaluate the expression of ZAP-70 in purified leukemic cells from chronic lymphocytic leukemia (CLL) patients. It was determined that the ZAP-70 expression level, which is high in T-cells, can be used to identify patients requiring certain treatments by assigning patients with CLL to the correct IgVH mutational subtype. High correlation concordance was shown for a spread of ZAP-70 mRNA levels between the DNA microarray and qRT-PCR assay. 34 The DASL TM (cDNA-mediated annealing, selection, extension, and ligation) assay to target gene-specific sequences was established using 16 FFPE samples from prostate, lung, colon, and breast tissues types. 35