Washington: A major challenge for cancer biologists had been to find out which among the hundreds of genetic mutations found in a cancer cell are most important for driving the cancer’s spread. But, now with a new technique MIT scientists have found the genes responsible for this.
Using whole-genome profiling, MIT scientists have pinpointed a gene that appears to drive progression of small cell lung cancer.
The gene, which the researchers found over expressed in both mouse and human lung tumours, could lead to new drug targets, said Alison Dooley, a recent PhD recipient in the lab of Tyler Jacks, director of MIT’s David H. Koch Institute for Integrative Cancer Research.
Dooley and her colleagues studied the disease’s progression using a strain of mice, developed in the laboratory of Anton Berns at the Netherlands Cancer Institute, that deletes two key tumour-suppressor genes, p53 and Rb.
“The mouse model recapitulates what is seen in human disease. It develops very aggressive lung tumours, which metastasize to sites where metastases are often seen in humans,” such as the liver and adrenal glands, said Dooley, lead author of a paper
Using whole-genome profiling, the researchers were able to identify sections of chromosomes that had been duplicated or deleted in mice with cancer.
They found extra copies of a few short stretches of DNA, including a segment of chromosome 4 that turned out to include a single gene called Nuclear Factor I/B (NFIB). This is the first time NFIB has been implicated in small cell lung cancer, though it has been seen in a mouse study of prostate cancer. The gene’s exact function is not known, but it is involved in the development of lung cells.
Researchers in Jacks’ lab collaborated with scientists in Matthew Meyerson’s lab at the Dana-Farber Cancer Institute and the Broad Institute to analyze human cancer cells, and found that NFIB is also amplified in human small cell lung tumors.
The NFIB gene codes for a transcription factor, meaning it controls the expression of other genes, so researchers in Jacks’ lab are now looking for the genes controlled by NFIB.
“If we find what genes NFIB is regulating, that could provide new targets for small cell lung cancer therapy,” Dooley said.
The study has been published in the Genes and Development.