cyclin-d1 and Osteolysis

Malignant melanoma is a relatively rare but potentially aggressive tumor in children and adolescents. We report the case of a metastatic malignant melanoma in a 17-year-old girl, first diagnosed on cytological features of a fine-needle lymph node aspiration and then histologically confirmed by both examination of the metastatic adenopathy and a clinically harmless skin lesion of the scalp, which harbored focal microscopic pattern of melanoma. A fluorescent in situ hybridization study revealed that both metastatic and primary cutaneous tumours contained the same and pejorative chromosomal aberration consisting in CCND1 amplification (11q13). This observation raises actual limits and challenges in the fields of diagnosis and treatment of fast-killing melanomas.

Topics: Adolescent; Antibodies, Monoclonal; Antineoplastic Agents, Alkylating; Back Pain; Combined Modality Therapy; Cyclin D1; Dacarbazine; Drug Resistance, Neoplasm; Fatal Outcome; Female; Gene Amplification; Head and Neck Neoplasms; Humans; Immunotherapy; In Situ Hybridization, Fluorescence; Ipilimumab; Lymphatic Metastasis; Melanoma; Nausea; Neoplasm Proteins; Neoplasms, Second Primary; Nevus; Osteolysis; Scalp; Skin Neoplasms; Weight Loss

The t(11;14)(q13;q32) is the most common translocation in multiple myeloma (MM), resulting in up-regulation of cyclin D1. We used a segregation fluorescence in situ hybridization (FISH) assay to detect t(11;14) breakpoints in primary MM cases and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify cyclin D1 and MYEOV (myeloma overexpressed) expression, another putative oncogene located on chromosome 11q13. High levels of cyclin D1 mRNA (cyclin D1/TBP [TATA box binding protein] ratio > 95) were found exclusively in the presence of a t(11;14) translocation (11/48 cases; P <.00001). In addition, a subgroup of MM cases (15/48) with intermediate to low cyclin D1 mRNA (cyclin D1/TBP ratio between 2.3 and 20) was identified. FISH analysis ruled out a t(11; 14) translocation and 11q13 amplification in these cases; however, in 13 of 15 patients a chromosome 11 polysomy was demonstrated (P <.0001). These results indicate an effect of gene dosage as an alternative mechanism of cyclin D1 deregulation in MM. The absence of chromosome 11 abnormalities in 2 of 15 patients with intermediate cyclin D1 expression supports that there are presumably other mechanism(s) of cyclin D1 deregulation in MM patients. Our data indicate that deregulation of MYEOV is not favored in MM and further strengthens the role of cyclin D1 overexpression in lymphoid malignancies with a t(11;14)(q13;q32) translocation.

Topics: Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; Gene Dosage; Humans; In Situ Hybridization, Fluorescence; Multiple Myeloma; Oncogene Proteins; Osteolysis; Proto-Oncogene Proteins; RNA, Messenger; Translocation, Genetic

Topics: Cyclin D1; Gene Expression; Humans; Intercellular Signaling Peptides and Proteins; Multiple Myeloma; Oligonucleotide Array Sequence Analysis; Osteolysis; Proteins; RNA, Messenger; Translocation, Genetic

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclin D1; Diagnosis, Differential; Female; Groin; Humans; Multiple Myeloma; Osteolysis; Pain; Radiography; Reverse Transcriptase Polymerase Chain Reaction; Skull