DNA mutations and copy number alterations identified in FFPE tumor samples suggest potential therapeutic targets

Cani AK, Hovelson DH, et al. (2015) Next-gen sequencing exposes frequent MED12 mutations and actionable therapeutic targets in phyllodes tumors. Mol Cancer Res, 13(4):613–619.

Citation summary: Next generation sequencing was used to identify DNA mutations and copy number alterations in FFPE phyllodes tumor samples. Results were validated with Sanger sequencing and IDT PrimeTime® qPCR Assays.

Mar 27, 2015

Revised/updated Oct 7, 2015

Phyllodes tumors are rare breast tumors that involve both stromal (connective) and glandular tissue. They are classified as benign (~65% of cases), borderline (~25% of cases), or malignant (~10% of cases) based on histopathology, but this classification often does not predict disease progression.

Phyllodes tumors, regardless of classification, usually grow quickly and can recur. Malignant tumors can also metastasize (to the lung, bone, heart, and liver), which decreases survival rates. Current treatment guidelines for all patients with phyllodes tumors require wide surgical resection margins and continued follow-up care, but efficacious treatment options for phyllodes tumors that progress to metastatic disease are lacking. These tumors do not respond to hormone therapy and do not respond well to radiation therapy or the chemotherapy drugs normally used for breast cancer.

In the featured article, Cani et al. used genomic sequencing and mutational profiling to characterize phyllodes tumors, which will help refine diagnoses and discover potential druggable targets for malignant disease. More specifically, they used targeted next generation sequencing to analyze 126 genes for somatic molecular alterations in 15 formalin-fixed, paraffin-embedded (FFPE) phyllodes tumors (5 of each classification).

Sanger sequencing was used to validate somatic variants [for example, mutations in the mediator complex subunit 12 (MED12), p53, retinoblastoma, and neurofibromin 1 genes], and PrimeTime® qPCR Assays that included ZEN Double-Quenched Probes were used to validate copy number alterations (for example, copies of the IGF1R and EGFR genes).