Abstract 1129P
Background
Cytogenetic studies reveal a large amount of chromosomal aberrations in 95% of melanoma cases. The goal of this study was to evaluate the prognostic significance of the most common chromosomal copy number alterations in melanomas with and without metastasis.
Methods
We investigated the association between copy number alterations, both gains and losses, and clinical outcome in 400 melanoma patients from the Cancer Genome Atlas (TCGA) cohort (89 had stage I, 117 stage II, 144 stage III and 20 stage IV) after a median 4-year follow-up. The data analysis was done using clinical and genetic TCGA datasets available at cbioportal.org. Copy number alterations were identified using data on chromosome-arm-level across the entire genome in tumor samples (primary 62%, regional 32%, and distant 16%). Survival distributions were estimated according to the method of Kaplan and Meier and the significance was tested with the log-rank statistic. Cox proportional hazards regression model were used to analyze the relationship between the frequency of copy number changes, tumor stage, and patient age.
Results
Chromosomal copy number losses were slightly more common than gains (2309 versus 1772); 13.47% and 10.52% of total copies analyzed respectively. Median aneuploidy score was 11 (range, 0-35 aberrations/tumor). The most frequent losses include deletions at 9p (60.35%), 10q (53.5%), 6q and 9q (47%). Frequent gains may occur at 7 (47%), 8q (42%), 1q (40.8%) and 6p (35.3%). The status of chromosome 9q was the only chromosomal alteration related to overall survival (OS) significantly in univariate analysis. Patients with 9p gain had a lower OS rate (43.8) than not call (78.9) or loss (94.9) months; p-0.018. A multivariate analysis identified young age <65 years (HR-0.5 p-0.0001; initial stages of disease: Stage I (HR-0.31 p-0.03) or Stage II (HR-0.38 p-0.016); and status of chromosome 9q (p-0.010): 9q loss (HR-0.42 p-0.005) as being independently associated with long survival.
Conclusions
Here, we provided functional evidence that copy number alterations of chromosome 9q are thought to play integral roles in melanoma prognosis. A targeted list of genes located in 9q could represent future prognostic molecular biomarkers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Medical Oncology Department from San Cecilio Universitary Hospital of Granada, Spain.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.