Long Noncoding RNA SAMMSON Linked to Malignant Melanoma
In collaboration with researchers from Ghent University, Vlaams Instituut voor Biotechnologie (VIB) scientists from the University of Leuven have revealed a remarkable link between malignant melanoma and a noncoding RNA gene called SAMMSON. The SAMMSON gene is specifically expressed in human malignant melanoma, and the growth of aggressive skin cancer is highly dependent on this gene. The conclusions could pave the way for improved diagnostic tools and targeted melanoma treatment. The study, led by Jean-Christophe Marine, PhD, and Pieter Mestdagh, PhD, was published by Leucci et al in Nature.
Key Findings
To assess the importance of specific long noncoding RNA (lncRNA) genes in skin cancer development, the VIB laboratory collaborated with the Department of Pediatrics and Medical Genetics at Ghent University. The Ghent researchers had performed a large screening to study the expression of numerous lncRNAs across different cancer types. This screening identified SAMMSON as a melanoma-specific lncRNA.
“Our research showed that the long noncoding RNA gene SAMMSON is specifically expressed in human melanomas and duplicated or amplified in about 10% of the cases. In addition, SAMMSON was nowhere to be found in melanocytes, the normal melanin-producing cells, nor in any other normal adult tissue. This unique expression profile of SAMMSON led us to hypothesize that this gene might play an important role in the etiology of melanoma,” said Dr. Mestdagh.
The VIB team confirmed that SAMMSON is expressed specifically in more than 90% of human malignant—and not in benign—melanoma clinical samples. In addition, they showed that the SAMMSON gene is activated by the melanoma-specific transcription factor SOX10, explaining its melanoma specific expression pattern.
Melanoma Addiction to SAMMSON
Moreover, the VIB scientists discovered a remarkable dependency of melanoma cells on SAMMSON expression. When reducing the presence of SAMMSON in melanoma cultures, cancer cells rapidly and massively die off, irrespective of the type of melanoma. This led to the key conclusion of a “SAMMSON addiction”.
“In both in vitro and preclinical studies in mice, we have proven that blocking SAMMSON through targeted antisense molecules drastically reduces the growth of melanoma. Importantly, we have also discovered that SAMMSON is recruited to mitochondria…by promoting degradation of SAMMSON, these antisense molecules disrupt the vital mitochondrial activity, which stops the tumor's growth…SAMMSON addiction is a clear vulnerability that we can combat through targeted therapy, without affecting the normal cells from the host or patient,” said Dr. Marine.
Study Implications
Further research will be necessary to firmly establish the study's hypothesis that SAMMSON can serve as a biomarker of melanoma malignancy. As the SAMSSON gene is not expressed in benign melanoma, its occurrence could be a key factor in developing new diagnostic tools that may dramatically improve melanoma prognosis.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
