A variant of the KLF6 tumor suppressor gene has been implicated in a recent study as a key driver of breast cancer metastasis that distinguishes between indolent and lethal early-stage disease. The variant, KLF6-SV1, provides a potential therapeutic target for invasive breast cancer.

The incorrect splicing of the KLF6 gene essentially creates a protein that causes cancer cells to metastasize. When a team led by Goutham Narla, MD, PhD, of Case Western Reserve University School of Medicine and the University Hospitals Seidman Cancer Center in Cleveland, Ohio, examined 671 breast cancer tumors from a tumor bank in The Netherlands, they found that persons whose tumors expressed high levels of KLF6-SV1 were 50% more likely to die than were other patients.

“We demonstrate that KLF6-SV1, an oncogenic splice variant of the KLF6 tumor suppressor gene, is associated with increased metastatic potential and poor survival in a cohort of 671 lymph node–negative breast cancer patients,” Narla and fellow investigators wrote in Science Translational Medicine.


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In a statement from University Hospitals Case Medical Center, Narla explained that the study presented biological proof that this splice variant can potentially be a marker for determining which patients with early-stage breast cancer will have disease progression. “More studies need to be done, but this could provide an important prognostic marker to determine which patients need to be treated more aggressively or watched more closely,” he affirmed.