Analysis of telomere length in mantle cell lymphoma

Mantle cell lymphoma (MCL) is a well defined lymphoid neoplasm genetically characterized by the t(11;14)(q13;q32). Telomeres play an essential role in preserving chromosomal integrity and genomic stability; their shortening can lead to telomere dysfunction and chromosomal instability, a critical factor in cancer development. In this study, telomere length (TL) measured by terminal restriction fragments (TRF) assay in DNA samples of tumor cells from 20 patients with MCL was evaluated. Results were correlated with clinical, morphologic and cytogenetic characteristics. In all cases, the presence of the CCND1/IGH rearrangement was confirmed by fluorescence in situ hybridization and/or PCR analysis. TL in total MCL patients revealed a mean TRF value (4.51 ± 0.79 kb) significantly shorter than those observed in controls (7.49 ± 1.94 kb) (P < 0.001); 30% of patients had TL shorter than 4.0 kb. TRF length was not associated with patients age (P = 0.07; r = 0.17) nor with sex (females: 4.33 ± 0.51 kb and males: 4.57 ± 0.85 kb; P = 0.63). No significant differences were found between patients studied at diagnosis (13) (4.44 ± 0.81 kb) respect to those analyzed at relapse (7) (4.63 ± 0.82 kb) (P = 0.53). In addition, we compared patients with (4.84 ± 1.09 kb) and without (4.40 ± 0.68 kb) complex karyotypes (P = 0.45) and cases with typical morphology (4.48 ± 0.79 kb) vs. blastoid variant (4.63 ± 1.04 kb) (P = 0.83), and no significant differences between them were found. Although the number of cases of our series is not large, our results showed that TL reduction in MCL is independent of the clinical characteristics, morphology and karyotype. © 2009 John Wiley & Sons A/S.Fil: Cottliar, Alejandra S. H.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Pedrazzini, Estela Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Noriega, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Narbaitz, Marina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Rodríguez, Andrea. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentin

Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis

Background and Aims: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites. Methods: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). Results: Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. Conclusion: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Cottliar, Alejandra S.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: La Motta, Graciela. Hospital San Martin; ArgentinaFil: Crivelli, Adriana. Hospital San Martin; ArgentinaFil: Gómez, Juan Carlos. Hospital San Martin; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentin