January 22, 2014
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Lung, colorectal cancers share ALK, ROS1 oncogenes

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Molecular alterations of ALK and ROS1, which have been identified in subsets of patients with lung cancer, can also present in patients with colorectal cancer, according to study results.

Dara Aisner, MD, PhD, an investigator at the University of Colorado Cancer Center and molecular pathologist at the University of Colorado School of Medicine, and colleagues sought to identify activated ALK and ROS1 tyrosine kinases — which respond well to therapy with selective kinase inhibitors in patients with lung cancer— in 236 tumor samples from patients with colorectal cancer.

“By rethinking the way we understand cancers — as their genetic mutations and not just as the sites where they live in the body — we see that a therapy that targets a specific mutation may show benefit in treating any other cancer that shares the same mutation,” Aisner said in a press release.

Researchers evaluated the samples using a four-target, four-color break-apart fluorescence in situ hybridization assay.

Among the samples, one demonstrated ALK rearrangement, and two others demonstrated ROS1 rearrangement.

Researchers identified EML4 as the fusion partner for the ALK rearrangement. In one of the samples that demonstrated ROS1 rearrangement, they identified SLC34A2 as the fusion partner. The fusion partner of the second ROS1 sample has yet to be identified.

In the ALK-positive sample, researchers also identified mutated KRAS. They noted that this specimen also marked intra-tumoral heterogeneity, and ALK rearrangement also was present in regions of high-grade dysplasia.

In addition, they found mutated BRAF in one sample with rearranged ROS1.

“This is a case in which we have all the background science — we know that when ALK and ROS1 improperly fuse with other genes, the result can be oncogenic,” Aisner said. “We have drugs that target these oncogenes. And we even have tests to determine who has the gene rearrangements and [therefore] should benefit from these drugs. The important piece missing was finding these oncogenes in other cancers, and now we’ve filled in that piece in colorectal cancer.”

Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.