Understanding Skin Cancer
Lund, August 13, 2018
The deadliest form of skin cancer, melanoma, is currently diagnosed by measuring its thickness to determine how far it has progressed and whether surgery alone will be enough to eliminate the cancer. The thicker the melanoma, the greater the risk that it has already begun spreading to other parts of the body. But this approach is not very reliable. Using HoloMonitor together with the latest gene editing techniques, scientists at University of California San Francisco (UCSF) have been able to explain why some thin melanomas metastasize and some thick ones do not.
Like cancerous tumors, common skin moles (swe: leverfläckar) are the result of genetic mutations. Unlike tumors, moles stop growing because a gene called CDKN2A halts the growth of moles. As previously shown by the UCSF researchers, it is first when this growth suppressor gene later in life is disabled by an additional mutation that a mole resumes growth and develops into invasive melanoma.
The nucleus of our cells contains the 23 chromosome pairs that make up our genome. A gene is a section of DNA in one of the chromosomes that has a specific biological function. A mutation is a DNA modification that potentially changes the biological function of a gene. Mutations can spontaneously occur when the gene is erroneously duplicated during cell division. Mutations can also occur through radiation, viral infections or by other external means.
A first mutation in the BRAF gene results in a mole. A mutation later in life in the CDKN2A gene results in invasive melanoma. The BRAF oncogene is located in chromosome 7 and the tumor suppressor gene CDKN2A is located in chromosome 9.
Using HoloMonitor technology and its ability to measure cell movement and cell proliferation (increase in cell number), the UCSF researchers have now also shown that a mutated and disabled CDKN2A gene not always results in resumed mole growth, as previously assumed. Instead, the mutation consistently results in hyper-motile (swe: hyperrörligt) and invasive cell behavior — explaining why both thick and thin melanomas metastasize. These and previous discoveries by UCSF researchers promise to significantly improve clinical melanoma assessment (swe: bedömning) by employing genetic assessment, rather than the less reliable thickness-based assessment which is currently used.
The latest discoveries involving HoloMonitor were recently published here in the prestigious and high-profile journal Cancer Cell. Cancer Cell publishes reports of novel results in any area of cancer research, from molecular and cellular biology to clinical oncology. The published work should be not only of exceptional significance within its field but also of interest to researchers outside the immediate area.
Additional reading
Evolution of Melanoma Reveals Opportunities for Intervention, UCSF News Center
References
- Bi-allelic Loss of CDKN2AInitiates Melanoma Invasion via BRN2 Activation, Cancer Cell
- The Genetic Evolution of Melanoma from Precursor Lesions, The New England Journal of Medicine
- Are moles determined by genetics?, Genetics Home Reference, U.S. National Library of Medicine
- Penn Scientists Identify Key Genetic Factor That Keeps Moles From Turning Into Melanoma, Penn Medicine News
