During normal cell division, Telomeres (nucleoprotein structures situated at the ends of chromosomes) shorten with each division and can potentially result in cell death, however, in some cancers this shortening is counteracted by the ALT mechanism and therefore permitting unlimited growth of cancer cells.
Research leader Christopher Heaphy, PhD, a postdoctoral research fellow at The Johns Hopkins School of Medicine said:
"The present study offers a springboard to guide future investigations in larger cohorts that specifically focus on the tumor types exhibiting ALT to more precisely determine the prevalence and potential prognostic value of this phenotype."
Heaphy's colleague, Alan K. Meeker, PhD, Assistant Professor of Pathology at Johns Hopkins, commented:
"These results may have therapeutic consequences, given that cancers using the ALT pathway are predicted to be resistant to anti-telomerase therapies, some of which have entered phase I/II clinical trials. Further understanding of the molecular mechanisms of ALT will be paramount in designing novel anti-cancer therapeutics targeting cancers utilizing the ALT pathway."
The researchers examined the predominance of the ALT mechanism in a large variety of human cancer subtypes by examining 6,110 tumor samples from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples, and discovered an overall prevalence of the ALT phenotype of 3.73%.
The ALT phenotype was neither observed in benign neoplasms nor in normal tissues. This is also the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes.
According to the researchers, they also identified many tumor types that possibly do not use the ALT pathway for telomere maintenance. During their examinations of hundreds of cases of adenocarcinomas arising from the prostate, colon, pancreas, or small intestine, they did not observe a single ALT-positive tumor.
Earlier studies revealed links between ALT status and prognosis in some tumor types. The authors recommend conducting further studies in order to evaluate the potential prognostic significance and unique biology of ALT-positive tumors.
Written by Petra Rattue