Genetic Drivers Found in Skin Cancer Development
Basal cell carcinoma is the cancer with the highest mutation rates.
Additional cancer genes have been found to drive the development of basal cell carcinoma (BCC).
Geneticists from the University of Geneva (UNIGE) sequenced the DNA of skin cancer tumors in order to identify which genes were responsible for causing BCC.
The study used 293 tumors from 236 patients of varying ages in order to sequence the genome of BCC tumors and compare it to the genetic profile of cells in healthy patients.
“It has been known for quite a while that a vast majority of BCCs are caused by abnormal activation of the so-called Sonic Hedgehog (SHh) pathway,” said head researcher Stylianos Antonarakis. “What we did not know was that BCC is also the cancer with the highest mutation rates. In addition to SHh, numerous other genes can contribute to this skin cancer, which evidently complicates the treatment.”
The results of a study published in Nature Genetics found that the genes MYCN, PTPN14, and LATS1 act as additional drivers for the development of BCC.
“We have developed a sophisticated statistical analysis software that permits us to localize the cancerous genes among the thousands of somatic mutations in the cancer DNA sequence,” said Sergey Nikolaev. “Once identified, we further tested their role as cancer drivers, for example by looking at molecules with and without mutations and comparing their structure and function.”
These findings were confirmed by studies of patients with Gorlin syndrome, which involves a molecular predisposition to developing BCCs early in life, and whose tumor DNA contains these additional genes.
“Cells respond differently to different ways of treatment because of the mutations of their genes,” Antonarakis said. “Some develop a resistance to certain drug substances, which renders the medication effect less. The additional mutations we detected could help in getting the best possible treatment results.”
“We suggest to sequence the healthy DNA and that of the tumor of each patient to really know which genes are responsible for the development of cancer,” Nikolaev added.