Foundation Medicine Inc., a molecular information company that brings comprehensive cancer gene analysis to routine clinical care, and Dana-Farber Cancer Institute announced the results from their collaborative next-generation sequencing (NGS) study to assay cancer-relevant genes in 24 non-small cell lung cancer (NSCLC) and 40 colorectal cancer (CRC) cases.

In the study, 59% of the samples were found to have genomic alterations directly associated with a clinically-available targeted therapeutic or a relevant clinical trial of a targeted therapy. Two novel gene fusions, KIF5B-RET in NSCLC and C2orf44-ALK in CRC, were discovered among the potentially drug-able alterations identified in the study. Both of the findings may expand therapeutic options for a subset of cancer patients, and demonstrates that using targeted NGS to profile patient tumors for molecular alterations associated with therapeutic responses may have a clinical impact in cancer treatment.

“In this collaboration, we detected clinically-relevant genomic alterations in more than half of the samples profiled, and, because Foundation Medicine’s NGS assay detects all classes of alterations with clinical-grade sensitivity, the research was able to identify both expected as well as completely novel alterations,” says Maureen Cronin, PhD, senior vice president, Research and Product Development of Foundation Medicine.

Clinically-relevant alterations were identified in 72% of NSCLC tumor samples and 52.5% of CRC tumor samples. The novel, recurrent KIF5B-RET fusion was identified by the NGS assay in one patient with NSCLC. In subsequent screening, 11 additional RET fusions were identified in 561 lung adenocarcinoma samples from a cohort of never or limited former smokers with NSCLC. In common with known oncogenic alterations in EGFR and EML4-ALK, the KIF5B-RET gene fusion was found more than twice as often in NSCLC samples from individuals of Asian descent. Additionally, none of the fusion-positive tumors contained alterations in any of the other known oncogenes that drive lung cancer (EGFR, ERBB2, BRAF or KRAS or rearrangements of EML4-ALK or ROS1). Tumors with the fusion were specifically sensitive to targeted drugs that inhibit RET, suggesting that prospective clinical trials of RET-targeted therapeutics may benefit individuals with NSCLC with KIF5B-RET rearrangements.

The second novel finding in the study was a potentially clinically-relevant gene fusion between C2orf44 and ALK identified in one CRC patient. Additional assays suggest the fusion gene yields 90-fold overexpression of anaplastic lymphoma kinase (ALK), the target of crizotinib, an FDA approved therapy for NSCLC. Given the structure of the rearrangement that generated the C2orf44-ALK fusion, it is unlikely that current clinical detection methods would have detected the alteration. The research suggests that a previously unrecognized subset of individuals with CRC may harbor genetic alterations that may make them responsive to ALK-inhibitor treatment.

The research was published in Nature Medicine.

Release Date: Feb. 12, 2012
 Source: Foundation Medicine