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Genetic analysis shows progression of moles to melanoma

16 November 2015

By Meetal Solanki

Appeared in BioNews 828

Researchers in the USA have mapped the sequence of genetic changes from early skin lesions, such as common moles, to malignant skin cancer, demonstrating the existence of an intermediate category in which lesions are neither benign or malignant.

The study, published in the New England Journal of Medicine, also demonstrated the already documented belief that continued ultra violet (UV) damage to benign lesions, such as by exposure to sunlight, can cause them to become malignant.

Moles normally have harmless genetic mutations, which are not dangerous, but the accumulation of additional mutations can push them to become cancerous. These genetic changes can be caused by UV radiation, which causes DNA damage, and gene mutations. However, for cells to become cancerous these mutations have to affect certain genes involved in the regulation of the multiplication of cells within one cell.

'The overwhelming majority of moles do not turn into melanoma. You need all the pathogenic mutations, and you have to have all those mutations in the same cell. That is highly unlikely to occur', said Professor Boris Bastian of the University of California, San Francisco (UCSF), a pathologist who co-led the study. However, the precise sequence of genetic changes that lead to melanoma is poorly understood.

In order to identify the stages of melanoma progression, researchers at UCSF gathered skin samples from 37 patients, containing both precursor lesions and melanoma, and searched for almost 300 cancer-causing genes. They then compared the results of the genetic sequencing with standard techniques of melanoma diagnosis that categorise cellular characteristics are being benign or malignant.

As expected, in all of the areas that were assessed by pathologists as benign, the genetic analysis found only one pathogenic mutation associated with melanoma. Likewise for melanomas categorised by cellular assessment as invasive, genetic analysis showed a significant number of mutations.

However, the most intriguing result of the study was the establishment of an intermediate category, in which precursor skin lesions had ambiguous cellular characteristics and were hard to categorise by traditional methods. The genetic profile of these lesions, however, set them apart from being either benign moles or invasive melanomas.

Most of these lesions in this category had the type of mutation seen in all benign moles, but additional pathogenic mutations were also observed - although these were minor compared to the host of mutations found in the invasive melanoma samples.

The researchers say the results could lead to the creation of genetic tests to assist healthcare professionals in detecting early melanoma formation.

'What happens to patients now is totally unstandardised,' said Professor Bastian. 'Some doctors consider these "intermediate" types of lesions to be entirely benign, or shave off only part of the lesion and leave some behind. But others treat it as an early melanoma. This work should open the door to understanding how risky these lesions are and when they should be completely removed.'

SOURCES & REFERENCES
GenomeWeb | 12 November 2015
 
NBC News | 12 November 2015
 
University of California San Francisco (press release) | 11 November 2015
 
Medscape | 11 November 2015
 
New England Journal of Medicine | 12 November 2015
 

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