by ecancer reporter Janet Fricker

Novel fusion genes found in lung and colorectal cancer tumour samples could open the way for new therapeutic options, suggests a US study in Nature Medicine.

In an earlier study the investigators from Dana-Farber Cancer Institute had identified a novel fusion gene in a tumour sample removed from a 44 year old man with non-small cell lung cancer (NSCLC) who had never smoked. 

The hybrid gene was composed of a piece of the cell growth gene RET, together with part of another gene - KIF5B. The fusion RET-KIF5B was responsible for RET acting like a growth “switch” for uncontrolled cell divisions.

In additional studies, when the investigators sequenced DNA samples from patients with colorectal cancer (CRC), along with the known mutations they identified a second novel gene alteration where the gene  C2or44 was combined with the ALK gene, causing over expression of the ALK protein leading to cancerous proliferation.

In the current study the team from the Dana-Farber Cancer Institute and Foundation Medicine INC, undertook next generation sequencing (NGS) study to assay cancer relevant genes in 24 non-small cell lung cancers (NSCLC) and 40 colorectal cancer (CRC) samples.

Overall the researchers found that 52.5% of subjects with CRC and 71% with NSCLC had genomic alterations directly linked to available therapeutic options, including the two novel gene fusions KIF5B-RET in NSCLC and C2orf44-ALK in CRC.

Cancers with similar genetic alterations to KIF5B-RET and C2orf44-ALK  have been shown to be targeted by tyrosine kinase inhibitors, suggesting that the same drugs might have the potential to be effective against lung and colorectal tumours.

While the researchers have estimated that less than 1 % of Caucasians and around 2 % of Asians with lung cancer carry the fusion gene labelled KIF5B-RET, they  still believe that the approach could prove helpful.

“In a common indication like NSCLC, identifying even a small subpopulation of individuals with gene fusions who may be responsive to a targeted therapy has the potential for a major therapeutic impact,” said Phillip Stephens, from Foundation Medicine Inc, who was one of the co-authors of the study.

Reference

D Lipson, M Capelletti, R Yelensky, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nature Medicine. Doi: 10.1038/nm.2673