Gene sequencing could identify genetic variants of lung cancer and colorectal cancer

By Dr. Ananya Mandal, MDFeb 14 2012

Foundation Medicine Inc., a molecular information company that brings comprehensive cancer gene analysis to routine clinical care, and Dana-Farber Cancer Institute have come up with 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.

They report their study in Nature Medicine. They note, that 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.

“It is moving closer and closer to real personalized medicine,” Janne, a lung cancer specialist at Dana-Farber, said in an interview. “It is fantastic as we can tailor our therapy to the particular genetics of a patient’s cancer.”

“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, senior vice president, Research and Product Development of Foundation Medicine.

They found that clinically relevant alterations can be 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 (0.8% (1/212) of the Caucasian samples and 2% (9/405) of the Asian patient samples).

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. 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.

Pfizer is aware of the new lung cancer gene finding and “believes the data are interesting,” said Jenifer Antonacci, a company spokeswoman, in an e-mail. Laura Woodin, a spokeswoman for London-based AstraZeneca, said the company “is constantly alert to new developments and research in the science of oncology and we review relevant, peer reviewed studies for what they might mean for patients and drug development.”