ABSTRACT
8p21.3 deletion was recently characterized in B cell lymphoma suggesting that TRAIL-R1 and TRAIL-R2 may be the target of the deletion and act as dosage-dependent tumor suppressor genes. As multiple myeloma is a plasma cell malignancy originating from B-lineage clonogenic cells, the idea was why do not evaluate this deletion in this pathology. Thus, interphase FISH studies with two mixtures of probes spanning the 8p21.3 region were retrospectively performed in 37 French multiple myeloma patients. Surprisingly, deletion in this region was found in 8 (21.6 %) patients. Interestingly, this deletion was usually associated with a 13q14 deletion. In two among them, the patients showed also translocation (4;14)(p16;q32) and one other harbor also a deletion of the P53 gene. These results indicate that deletion of TRAIL-R1 and TRAIL-R2 may be relevant to the loss of 8p21.3 and may play an important role the pathogenesis of MM. The association of this deletion with other well-known chromosomal aberrations in multiple myeloma suggests, as previously described, that these anomalies are not randomly distributed, but strongly interconnected.
Subject(s)
Genes, Tumor Suppressor/physiology , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Aged , Biomarkers, Tumor/genetics , Chromosome Deletion , Chromosomes, Human, Pair 8/genetics , Cohort Studies , Female , Genetic Association Studies/methods , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Cytogenetic studies in multiple myeloma (MM) are hampered by the hypo-proliferative nature of plasma cells. In order to circumvent this problem, we have used a combination of immunolabeling of cytoplasmic Ig light chains (λ or κ) and FISH (cIg-FISH), which allowed a comprehensive detection of the most common and/or recurrent molecular cytogenetic aberrations on fixed bone marrow cells of 70 Tunisian patients. Translocations involving the chromosome 14q32 region were observed in 32 cases (45.7%), including 18 cases with a t(11;14), 8 cases with a t(4;14), and 2 cases with a t(14;16). Deletions of the 13q14 region (D13S319/RB1) were detected in 18.6%, and deletions of the 17p13 region (TP53) in 5.7% of the cases, respectively. Of all patients with a D13S319/RB1 deletion, 61.5% also carried a 14q32 translocation, whereas TP53 deletions were associated with a t(11;14) in 2 cases (50%) and a D13S319 deletion in 1 case (25%). Our results suggest that there is a correlation between the presence of 14q32 translocations and chromosome 13q14 deletions in MM patients and that cIg-FISH is more sensitive as compared to conventional karyotyping in detecting molecular cytogenetic abnormalities in this disease.
Subject(s)
Bone Marrow Cells/ultrastructure , Chromosome Aberrations , Multiple Myeloma/genetics , Adult , Aged , Child , Chromosome Deletion , Chromosomes, Human, Pair 13 , Chromosomes, Human, Pair 14 , Cytogenetic Analysis/methods , Female , Humans , Immunoglobulin Heavy Chains/genetics , In Situ Hybridization, Fluorescence/methods , Karyotyping/methods , Male , Middle Aged , Multiple Myeloma/metabolism , Translocation, Genetic , TunisiaABSTRACT
The aim of this study was to evaluate the incidence of spermatic aneuploidies in men with severe teratozoospermia and to determine an eventual relation between aneuploidies and a specific morphology of spermatozoa. Fluorescence in situ hybridisation (FISH) using a probe cocktail containing the alpha satellite for the centromeric region of chromosome X, Y and 18 was performed on decondensed spermatozoa from fresh ejaculates of thirty patients with severe teratozoospermia (abnormal forms >80%) and 15 fertile men with normal semen profiles. The mean frequency of teratozoospermia in patients was 91 ± 6.99%. There was statistically a significantly increased frequency of 1818, XY, XX and YY disomies in sperm with severe teratozoospermia compared with normal sperm (1.24% versus 0.08%, 1.42% versus 0.31%, 1.13% versus 0.19% and 1.11% versus 0.24%, respectively, P < 0.001 in all comparisons). The rate of total diploidy was significantly increased in patients compared with controls (1.46% versus 0.16%, P < 0.001). There was a correlation between macrocephalic spermatozoa and diploidy (r = 0.37, P < 0.05). Our data add further evidence that patients with severe teratozoospermia have an increased sperm aneuploidy rate and that this is particularly high in macrocephalic spermatozoa; FISH analysis on sperm could help to improve risk assessment and reproductive counselling in these individuals who are frequently candidates for intracytoplasmic sperm injection (ICSI) as a treatment of their infertility, as the use of ICSI has created consequential debate concerning the genetic risk for the offspring.
