Visualizing a genome in disarray
Top, Spectral karyogram of normal human male chromosomes. Image by
Nallasivam Palanisamy, Ph.D., Michigan Center for Translational Pathology.
Bottom, Spectral karyogram of a breast cancer cell line. Image by Mira
Grigorova and Paul Edwards, unpublished.
Last week on the Broad website, we featured recent work by Broad researchers that can shed new light on the massive genomic changes taking place in cancer cells. The genomes in tumors are often drastically disorganized, with large chunks of missing or extra DNA — even whole chromosomes — in addition to smaller, single-letter mutations. These alterations can complicate the search for genetic changes underlying cancer.
The Broad research team created a new computational method, ABSOLUTE, that infers the “ploidy” – the number of sets of chromosomes in each cell – from relative measures of DNA mass to calculate genetic changes on an absolute (per-cell) basis, giving a more informative picture of the alterations in cancer cells.
Although ABSOLUTE gives a new window into the disarray within a cancer cell, scientists have been peering at chromosomes in chaos for more than a hundred years. In 1888, long before researchers knew about DNA or genes, and even before the word chromosome existed, Theodor Boveri noticed that the chromosomes of human cancers were often scrambled and proposed a theory for the chromosomal basis of cancer. (Boveri made an astounding number of insights that would eventually be confirmed when modern molecular biology caught up with him – his 1908 paper remains an intriguing read for many biologists today.)
Aneuploidy, or an abnormal number of chromosomes, is found in many cancers. This phenomenon is well illustrated by the spectral karyogram, an image that displays chromosomes “painted” with different fluorescent probes. These two spectral karyograms comparing a normal male genome and that of a breast cancer cell line demonstrate with vivid colors the striking changes that take place in the cancer genome.
ABSOLUTE allows scientists to infer these changes in genetic data from large-scale studies, representing a powerful new tool for analyzing cancer DNA. Read more about the new tool on the Broad’s news story.