ABSTRACT
Overcoming replicative senescence is an essential step during oncogenesis, and the reactivation of TERT through promoter mutations is a common mechanism. TERT promoter mutations are acquired in about 75% of melanomas but are not sufficient to maintain telomeres, suggesting that additional mutations are required. We identified a cluster of variants in the promoter of ACD encoding the shelterin component TPP1. ACD promoter variants are present in about 5% of cutaneous melanoma and co-occur with TERT promoter mutations. The two most common somatic variants create or modify binding sites for E-twenty-six (ETS) transcription factors, similar to mutations in the TERT promoter. The variants increase the expression of TPP1 and function together with TERT to synergistically lengthen telomeres. Our findings suggest that TPP1 promoter variants collaborate with TERT activation to enhance telomere maintenance and immortalization in melanoma.
Subject(s)
Melanoma , Promoter Regions, Genetic , Shelterin Complex , Skin Neoplasms , Telomerase , Telomere Homeostasis , Telomere-Binding Proteins , Humans , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Melanoma/genetics , Mutation , Promoter Regions, Genetic/genetics , Shelterin Complex/genetics , Skin Neoplasms/genetics , Telomerase/genetics , Telomere/genetics , Telomere/metabolism , Telomere Homeostasis/genetics , Telomere-Binding Proteins/genetics , Transcriptional ActivationABSTRACT
There are nearly 70,000 new cancer diagnoses made annually in adolescents and young adults (AYAs) in the United States. Historically, AYA patients with cancer, aged 15 to 39 years, have not shown the same improved survival as older or younger cohorts. This article reviews the contemporary cancer incidence and survival data through 2015 for the AYA patient population based on the National Cancer Institute's Surveillance, Epidemiology, and End Results registry program and the North American Association of Central Cancer Registries. Mortality data through 2016 from the Centers for Disease Control and Prevention's National Center for Health Statistics are also described. Encouragingly, absolute and relative increases in 5-year survival for AYA cancers have paralleled those of childhood cancers since the year 2000. There has been increasing attention to these vulnerable patients and improved partnerships and collaboration between adult and pediatric oncology; however, obstacles to the care of this population still occur at multiple levels. These vulnerabilities fall into 3 significant categories: research efforts and trial enrollment directed toward AYA malignancies, access to care and insurance coverage, and AYA-specific psychosocial support. It is critical for providers and health care delivery systems to recognize that the AYA population remains vulnerable to provider and societal complacency.
Subject(s)
Medical Oncology/trends , Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Humans , Incidence , Medical Oncology/methods , Neoplasms/psychology , Neoplasms/therapy , SEER Program , Survival Rate , United States/epidemiology , Young AdultABSTRACT
BACKGROUND: Lymphatic mapping to guide sentinel lymph node biopsy (SLNB) typically requires lymphoscintigraphy prior to surgery. In young pediatric patients, this process often requires intubation in the nuclear medicine suite followed by transport to the operating room (OR). METHODS: We reviewed 14 pediatric cases in which a portable nuclear imaging camera was utilized to perform the entirety of the SLNB in the OR. RESULTS AND CONCLUSION: This method, utilizing intraoperative nuclear imaging, helped to confirm removal of the sentinel lymph node in real time, decreased anesthesia time, and avoided transport of a sedated or intubated child. LEVEL OF EVIDENCE: III.
