Limits...
Microsatellite alterations are also present in the less aggressive types of adult T-cell leukemia-lymphoma.

Magalhães M, Oliveira PD, Bittencourt AL, Farre L - PLoS Negl Trop Dis (2015)

Bottom Line: The mechanisms that lead to the development of ATL clinical types have not yet been clarified.Four microsatellite markers D10S190, D10S191, D1391 and DCC were analyzed.MSI was found in four patients, three smoldering and one chronic, and LOH in four patients, three smoldering and one acute.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Pathology (LAPEX), Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPQGM/FIOCRUZ), Salvador, Bahia, Brazil.

ABSTRACT

Background: Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasia etiologically linked to HTLV-1. Manifestations of ATL are diverse and different clinical types with different tissue involvement and aggressiveness have been described. The mechanisms that lead to the development of ATL clinical types have not yet been clarified. Considering that in ATL patients HTLV-1 infection generally occurs in childhood, a multistep carcinogenesis model has been proposed. Microsatellite alterations are important genetic events in cancer development and these alterations have been reported in the aggressive types of ATL. Little is known about oncogenesis of the less aggressive types.

Methodology/principal findings: In this study we investigated the role of the microsatellite alterations in the pathogenesis mediated by HTLV-1 in the different types of ATL. We examined the presence of microsatellite instability (MSI) and loss of heterozigosity (LOH) in matched pair samples (tumoral and normal) of 24 patients with less aggressive types (smoldering and chronic) and in aggressive types (acute and lymphoma) of ATL. Four microsatellite markers D10S190, D10S191, D1391 and DCC were analyzed. MSI was found in four patients, three smoldering and one chronic, and LOH in four patients, three smoldering and one acute. None of the smoldering patients with microsatellite alterations progressed to aggressive ATL.

Conclusions/significance: To our knowledge, this is the first report describing the presence of MSI and LOH in the less aggressive types of ATL. These results indicate that microsatellite alterations may participate in the development of the less aggressive types of ATL.

Show MeSH

Related in: MedlinePlus

Assessment of microsatellite instability—MSI (a) and loss of heterozigosity—LOH (b) in patients with adult T cell leukemia-lymphoma (ATL).(a1) Tumor sample without allelic shift compared with normal sample (marker D10S191 – case 22). (a2) Patient showing allelic shift in tumor sample indicating the presence of microsatellite instability (D10S191 marker—case 8). (a3) Patient showing a novel allele in tumoral sample indicating the presence of microsatellite instability (marker D11S1391 – case 15). The arrows indicate allelic shift. (b1) The presence of a single peak in both normal and tumor DNA indicates a non informative case for LOH analysis (marker D10S190 – case 1). (b2) The presence of two peaks in normal and tumor DNA indicates an informative case for LOH analysis (marker D11S1391 – case 9). (b3) The decrease in peak height in one of two alleles in tumor DNA indicates allelic imbalance (LOH) (marker DCC – case 12); S, Size of PCR product (in pb); H, Fluorescence intensity of peak; A, area of peak.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4295852&req=5

pntd.0003403.g001: Assessment of microsatellite instability—MSI (a) and loss of heterozigosity—LOH (b) in patients with adult T cell leukemia-lymphoma (ATL).(a1) Tumor sample without allelic shift compared with normal sample (marker D10S191 – case 22). (a2) Patient showing allelic shift in tumor sample indicating the presence of microsatellite instability (D10S191 marker—case 8). (a3) Patient showing a novel allele in tumoral sample indicating the presence of microsatellite instability (marker D11S1391 – case 15). The arrows indicate allelic shift. (b1) The presence of a single peak in both normal and tumor DNA indicates a non informative case for LOH analysis (marker D10S190 – case 1). (b2) The presence of two peaks in normal and tumor DNA indicates an informative case for LOH analysis (marker D11S1391 – case 9). (b3) The decrease in peak height in one of two alleles in tumor DNA indicates allelic imbalance (LOH) (marker DCC – case 12); S, Size of PCR product (in pb); H, Fluorescence intensity of peak; A, area of peak.

Mentions: MSI was found in four of the 24 patients evaluated (16.6%) (Table 1; Fig. 1A), three of which consisted of smoldering and one of chronic ATL. Two patients were males and two females. In the smoldering ATL, MSI was found in only one locus, in chromosome 10 in two patients (in marker D10S190 in patient #6 and in D10S191 in patient #8) and in chromosome 18 in the other.


Microsatellite alterations are also present in the less aggressive types of adult T-cell leukemia-lymphoma.

Magalhães M, Oliveira PD, Bittencourt AL, Farre L - PLoS Negl Trop Dis (2015)

Assessment of microsatellite instability—MSI (a) and loss of heterozigosity—LOH (b) in patients with adult T cell leukemia-lymphoma (ATL).(a1) Tumor sample without allelic shift compared with normal sample (marker D10S191 – case 22). (a2) Patient showing allelic shift in tumor sample indicating the presence of microsatellite instability (D10S191 marker—case 8). (a3) Patient showing a novel allele in tumoral sample indicating the presence of microsatellite instability (marker D11S1391 – case 15). The arrows indicate allelic shift. (b1) The presence of a single peak in both normal and tumor DNA indicates a non informative case for LOH analysis (marker D10S190 – case 1). (b2) The presence of two peaks in normal and tumor DNA indicates an informative case for LOH analysis (marker D11S1391 – case 9). (b3) The decrease in peak height in one of two alleles in tumor DNA indicates allelic imbalance (LOH) (marker DCC – case 12); S, Size of PCR product (in pb); H, Fluorescence intensity of peak; A, area of peak.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295852&req=5

pntd.0003403.g001: Assessment of microsatellite instability—MSI (a) and loss of heterozigosity—LOH (b) in patients with adult T cell leukemia-lymphoma (ATL).(a1) Tumor sample without allelic shift compared with normal sample (marker D10S191 – case 22). (a2) Patient showing allelic shift in tumor sample indicating the presence of microsatellite instability (D10S191 marker—case 8). (a3) Patient showing a novel allele in tumoral sample indicating the presence of microsatellite instability (marker D11S1391 – case 15). The arrows indicate allelic shift. (b1) The presence of a single peak in both normal and tumor DNA indicates a non informative case for LOH analysis (marker D10S190 – case 1). (b2) The presence of two peaks in normal and tumor DNA indicates an informative case for LOH analysis (marker D11S1391 – case 9). (b3) The decrease in peak height in one of two alleles in tumor DNA indicates allelic imbalance (LOH) (marker DCC – case 12); S, Size of PCR product (in pb); H, Fluorescence intensity of peak; A, area of peak.
Mentions: MSI was found in four of the 24 patients evaluated (16.6%) (Table 1; Fig. 1A), three of which consisted of smoldering and one of chronic ATL. Two patients were males and two females. In the smoldering ATL, MSI was found in only one locus, in chromosome 10 in two patients (in marker D10S190 in patient #6 and in D10S191 in patient #8) and in chromosome 18 in the other.

Bottom Line: The mechanisms that lead to the development of ATL clinical types have not yet been clarified.Four microsatellite markers D10S190, D10S191, D1391 and DCC were analyzed.MSI was found in four patients, three smoldering and one chronic, and LOH in four patients, three smoldering and one acute.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Pathology (LAPEX), Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPQGM/FIOCRUZ), Salvador, Bahia, Brazil.

ABSTRACT

Background: Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasia etiologically linked to HTLV-1. Manifestations of ATL are diverse and different clinical types with different tissue involvement and aggressiveness have been described. The mechanisms that lead to the development of ATL clinical types have not yet been clarified. Considering that in ATL patients HTLV-1 infection generally occurs in childhood, a multistep carcinogenesis model has been proposed. Microsatellite alterations are important genetic events in cancer development and these alterations have been reported in the aggressive types of ATL. Little is known about oncogenesis of the less aggressive types.

Methodology/principal findings: In this study we investigated the role of the microsatellite alterations in the pathogenesis mediated by HTLV-1 in the different types of ATL. We examined the presence of microsatellite instability (MSI) and loss of heterozigosity (LOH) in matched pair samples (tumoral and normal) of 24 patients with less aggressive types (smoldering and chronic) and in aggressive types (acute and lymphoma) of ATL. Four microsatellite markers D10S190, D10S191, D1391 and DCC were analyzed. MSI was found in four patients, three smoldering and one chronic, and LOH in four patients, three smoldering and one acute. None of the smoldering patients with microsatellite alterations progressed to aggressive ATL.

Conclusions/significance: To our knowledge, this is the first report describing the presence of MSI and LOH in the less aggressive types of ATL. These results indicate that microsatellite alterations may participate in the development of the less aggressive types of ATL.

Show MeSH
Related in: MedlinePlus