Chromosome abnormalities in peripheral blood lymphocytes from untreated Hodgkin's patients

Barrios, Leonardo; Caballı́n, Marı́a Rosa; Miró, R.; Fuster, Carme; Berrozpe, Georgina; Subias, Antoni; Batlle, Xavier; Egozcue, J.

doi:10.1007/bf00291727

Cited by 47 publications

(19 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relationship between presence of high frequencies of chromosome aberrations and predisposition to cancer has been established in syndromes, such as ataxia telangiectasia, Bloom's syndrome, and Fanconi's anemia. However, a low level of chromosomal instability is also detectable in the peripheral blood lymphocytes of patients with skin, breast, and bladder cancers and lymphomas (25)(26)(27)(28)). An increased frequency of chromosome aberrations in circulating lymphocytes is generally considered indicative of increased cancer risk for those exposed to DNA-damaging agents.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

El‐Zein

Sierra

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Prostate cancer is an extremely complex disease, and it is likely that chromosomal instability is involved in the genetic mechanism of tumorigenesis. Several chromosomes have been labeled as “players” in the development of prostate cancer, among them chromosome 1 and X chromosome have been reported to harbor prostate cancer susceptibility loci. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures from 126 study subjects, 61 prostate cancer patients, and 65 healthy controls. We evaluated chromosomal instability using a fluorescence in situ hybridization assay using two probes targeting specific regions on X chromosome and chromosome 1. Our results showed a significantly higher mean level of spontaneous breaks involving the X chromosome in patients compared with controls (mean ± SE, 2.41 ± 0.26 and 0.62 ± 0.08, respectively; P < 0.001). Similarly, chromosome 1 spontaneous breaks were significantly higher among cases compared with controls (mean ± SE, 1.95 ± 0.24 and 1.09 ± 0.16, respectively; P < 0.001). Using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (95% confidence interval) of 15.53 (5.74 - 42.03; P < 0.001) for spontaneous X chromosome breaks and 3.71 (1.60 - 8.63; P < 0.001) for chromosome 1 breaks and risk of development of prostate cancer. In conclusion, our preliminary results show that spontaneous chromosome instability could be a risk factor for prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

El‐Zein

Sierra

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…In our study, we detected cells with GCR in two of five pretreatment patients that consisted of clones of 3 and 15 cells with del(7)(q36) and del(21)(q22), respectively (Table IV). These chromosomal abnormalities have been related to cytogenetic changes in cancerous Reed-Sternberg Hodgkin cells [Barrios et al, 1988;M'Kacher et al, 2003]. Interestingly, these cells may be related to viral infections which even 2 years after treatment, may generate chromosomal instability in the peripheral blood of patients [M'Kacher et al, 2010].…”

Section: Complex Structural Chromosome Damage Is Increased In Hl Survmentioning

confidence: 99%

Persistent genomic instability in peripheral blood lymphocytes from hodgkin lymphoma survivors

Salas-Labadía¹,

Niembro²,

Lozano³

et al. 2012

Environ and Mol Mutagen

View full text Add to dashboard Cite

Advances in cancer treatment have led to an increase in patient survival. However, exposure to genotoxic chemotherapeutic agents and ionizing radiation may induce persistent genetic damage in cancer survivors. In this study, we detected genomic instability in chromosomes of peripheral blood lymphocytes from Hodgkin lymphoma patients, 2–17 years after MOPP (nitrogen mustard, Oncovin, procarbazine, and prednisone) chemotherapy with or without radiotherapy. Samples were obtained from 11 healthy individuals, 5 pretreatment patients, and 20 posttreatment patients. Cytogenetic analysis with GTG banding was performed on 1,000 lymphocyte metaphases per donor to identify genomic instability, including numerical and structural chromosomal aberrations, at a resolution of 10 Mb across the entire genome. Our results showed that anticancer treatment did not induce significant differences in the frequency of aneuploidy among the three study groups. However, 1 of the 11 healthy individuals, and 13 of the 20 posttreatment patients had a high frequency of chromosomal breaks and gross chromosomal rearrangements. The types of aberrations observed were random and complex, consistent with persistent genomic instability that was induced by cancer treatment. Clonal expansion of cells with chromosomal lesions was observed in one posttreatment patient only. These findings show that anticancer treatments induce persistent genomic instability, but not aneuploidy. Chemotherapy may affect genes with a role in DNA damage surveillance or repair, which in turn allows the accumulation of nontargeted structural chromosomal damage in future generations of cells. This genomic instability may facilitate the development of second malignancies in Hodgkin lymphoma survivors. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.

show abstract

“…2). Notably, most genomic imbalances shared by at least 2 classic HL patients who developed AML were also found in aCGH set using DNAs ONCOLOGY REPORTS 18: 1427-1434, 2007 Table I. Clinical details of classic HL patients included in the study.…”

Section: Resultsmentioning

confidence: 99%

“…Virtually all H/RS cells exhibit neither clonal nor disease-specific chromosomal abnormalities that may originate from their own or their progenitor inherent genomic instability (3). The hypothesis of an unstable genetic background concurrently promoting the evasion of H/RS cell progenitors from FAS-mediated negative selection in the germinal centre, accumulation of multiple genetic aberrations driving their progression towards a fully transformed phenotype and deregulated differentiation culminating in endomitosis is advanced by the findings that chromosomal abnormalities (eventually resulting in oncosuppressor loss) are not restricted to the malignant cellular context (4)(5)(6)(7)(8). The association of polymorphisms in DNA repair and oxidative stress response genes with an increased risk for non-Hodgkin lymphoma supports a role of individual genetic susceptibility in primary B lymphomagenesis (9,10).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genomic imbalances associated with secondary acute leukemias in Hodgkin lymphoma

et al. 2007

View full text Add to dashboard Cite

Abstract. Secondary tumors and leukemias are major complications in Hodgkin lymphoma (HL). They likely arise from clonal selection of cells that have accumulated genomic lesions induced by chemo-and radiotherapy and may be further promoted by the loss of DNA repair and/or other pathways ensuring the fidelity of replicated DNA. To distinguish genomic imbalances associated with the development of acute myeloid leukemia (AML) in HL we used an array-based comparative genomic hybridization (aCGH) strategy on whole lymph node biopsies of HL patient. Genomic imbalances (amplifications and deletions) associated with AML outcome in 3 classic HL patients, at clinical diagnosis they exhibited a discrete individual variability. Three amplifications and 5 deletions were shared by all 3 patients. They involved AFM137XA11, a 9p11.2 pericentric region; FGFR1, the FGF receptor most frequently translocated in AML; PPARBP, a co-activator of nuclear receptors RARα, RXR and TRß1; AFM217YD10, a 17q25 telomeric region; FGR, an SRC2 kinase involved in cytokine production by NK and CD4 + NKT cells; GATA3, a Th2-specific transcription factor; TOP1, involved in DNA recombination and repair; WT1, a transcription factor involved in CD8 + T cell response against leukaemic blasts. Immunohistochemistry confirmed aCGH results and distinguished the distribution of either amplified or deleted gene products in neoplastic Reed Sternberg (RS) cells and nonneoplastic lymph node components.

show abstract

Chromosome abnormalities in peripheral blood lymphocytes from untreated Hodgkin's patients

Cited by 47 publications

References 30 publications

Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

Persistent genomic instability in peripheral blood lymphocytes from hodgkin lymphoma survivors

Genomic imbalances associated with secondary acute leukemias in Hodgkin lymphoma

Contact Info

Product

Resources

About