Discovery of Biomarker for Deadly Melanoma Skin Cancer Offers New Hope
Researchers were able to reverse melanoma growth in pre-clinical studies
Sept. 13, 2012 – Researchers claim discovery of a novel opportunity for melanoma skin cancer diagnostics, treatment and
prevention. Melanoma is the most dangerous of skin cancers, the leading cause of death from skin cancer and is increasing faster than any
other cancer. It most often strikes older people.
A new biomarker for the lethal disease has been discovered by researchers at Brigham and Women's Hospital (BWH). Teams led by Yujiang Geno Shi, PhD, from BWH's
Department of Medicine, and George F. Murphy, MD, from BWH's Department of Pathology made the discovery.
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Their study will be published on September 14, 2012 in Cell.
"Dr. Shi and colleagues have discovered an exciting new connection between the loss of a specific chemical mark in the
genome and the development of melanoma," said Anthony Carter, PhD, of the National Institutes of Health's National Institute of General
Medical Sciences, which mainly funded the research.
"This work is a prime example of how basic research on mechanisms of epigenetic regulation can yield clinically
significant insights that hold great promise for diagnosing and treating cancer."
The researchers found that certain biochemical elements in the DNA of normal pigment-producing skin cells and benign mole
cells are absent in melanoma cells. Loss of these methyl groups - known as 5-hmC - in skin cells serves as a key indicator for malignant
melanoma. Loss corresponded to more advanced stages of melanoma as well as clinical outcome.
Strikingly, researchers were able to reverse melanoma growth in pre-clinical studies. When the researchers introduced
enzymes responsible for 5-hmC formation to melanoma cells lacking the biochemical element, they saw that the cells stopped growing.
"It is difficult to repair the mutations in the actual DNA sequence that are believed to cause cancer," said Christine
Lian, MD, a physician scientist in the Department of Pathology at BWH and one of the lead authors.
Do You Have Melanoma?
Melanoma
is the most serious type of
skin cancer and senior citizens are the usual victims. Often the first sign of melanoma is a change in the size, shape, color or
feel of a mole. Most melanomas have a black or black-blue area. Melanoma may also appear as a new mole. It may be black, abnormal or
"ugly looking."
Thinking of "ABCD" can help you remember what to watch
for:
● Asymmetry - the shape of one half does not match the other
● Border - the edges are ragged, blurred or irregular
● Color - the color in uneven and may include shades of black, brown and tan
● Diameter - there is a change in size, usually an increase
Melanoma can be cured if it is diagnosed and treated early. If melanoma is not removed in
its early stages, cancer cells may grow downward from the skin surface and invade healthy tissue. If it spreads to other parts of the body it
can be difficult to control.
"So having discovered that we can reverse tumor cell growth by potentially repairing a biochemical defect that exists—not
within the sequence—but just outside of it on the DNA structure, provides a promising new melanoma treatment approach for the medical
community to explore."
Because cancer is traditionally regarded as a genetic disease involving permanent defects that directly affects the DNA
sequence, this new finding of a potentially reversible abnormality that surrounds the DNA (thus termed epigenetic) is a hot topic in cancer
research, according to the researchers.
In the United States, melanoma is the fifth most common type of new cancer diagnosis in men and the seventh most common
type in women. The National Cancer Institute estimates that in 2012 there will be 76,250 new cases and 9,180 deaths in the United States due
to melanoma.
The Shi laboratory pioneers studies in both basic chromatin biology and translational epigenetic research at the
Endocrine Division, BWH Department of Medicine, and collaborates with Dr. Murphy's laboratory that focuses on melanoma biology in the Program
for Dermatopathology, BWH Department of Pathology.
This pre-clinical study, which shows a key role for epigenetics in melanoma development and
progression, also enlisted the support of an international team of investigators.
The findings will provide insight for future functional, pre-clinical studies of 5-hmC in cancer biology.
This research was supported by the National Institutes of Health grant GM078458, SPORE Core: NIH-NCI SPORE in Skin Cancer
5P50CA093683-08, the BWH BRI Bridge Fund, and partly by the Chinese Ministry of Education Project 985.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding
member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs
nearly 15,000 people.
About Melanoma
Melanoma is a form of cancer that
begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other
pigmented tissues, such as in the eye or in the intestines.
It is estimated that 76,250 men and women (44,250 men and 32,000 women) will be diagnosed with and 9,180 men
and women will die of melanoma of the skin in 2012.
From 2005-2009, the median age at diagnosis for melanoma of the skin was 61 years of age.
Approximately 0.6% were diagnosed under age 20; 6.8% between 20 and 34; 10.7% between 35 and 44; 18.2%
between 45 and 54; 21.6% between 55 and 64; 18.8% between 65 and 74; 16.7% between 75 and 84; and 6.6% 85+ years of age.
The age-adjusted incidence rate was 21.0 per 100,000 men and women per year.
US Mortality
From 2005-2009, the median age at death for melanoma of the skin was 68 years of age. Approximately 0.1% died
under age 20; 2.6% between 20 and 34; 5.6% between 35 and 44; 13.5% between 45 and 54; 19.9% between 55 and 64; 21.2% between 65
and 74; 24.1% between 75 and 84; and 12.9% 85+ years of age.
The age-adjusted death rate was 2.7 per 100,000 men and women per year. These rates are based on patients who
died in 2005-2009 in the US.
Lifetime Risk
Based on rates from 2007-2009, 1.99% of men and women born today will be diagnosed with melanoma of the skin
at some time during their lifetime. This number can also be expressed as 1 in 50 men and women will be diagnosed with melanoma of
the skin during their lifetime. These statistics are called the
lifetime risk of developing cancer.
Sometimes it is more useful to look at the
probability of developing melanoma of the skin between two age groups. For example,
0.99% of men will develop melanoma of the skin between their 50th and 70th birthdays compared to 0.60% for women
Prevalence
On January 1, 2009, in the United States there were approximately 876,344 men and women alive who had a
history of melanoma of the skin - 427,810 men and 448,534 women.
Senior Citizens major targets of skin cancer; bout
one in five 70-year-olds have had non-melanoma skin cancers, and most
who were affected have had more than one
Couples encouraged to examine each other for
suspicious moles that could be skin cancer. Researchers estimate that 40
– 50% of people in the U.S. who live to age 65 will have nonmelanoma
skin cancer at least once.
Researchers say they have found why treatment is difficult and may have answer for
turning this around
"We win because we care, we prepare
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