Cancer cytogenetics update 2005

Deep insight on Cancer cytogenetics update 2005

Aberrations of chromosome No. 1 in blastic phase of chronic myeloid leukemia

Aberrations of chromosome No. 1 were detected at the time of blastic crisis in 7 patients with Ph1-positive chronic myeloid leukemia (CML). Two patients had trisomy 1; trisomy for a long arm segment of chromosome No. 1 was present in 2 patients; trisomy for a short arm segment occurred in 2 patients; and one patient had an apparently balanced translocation affecting chromosome No. 1. All patients with extra material of chromosome No. 1 were trisomic for the region 1p22–1pter or 1q21–1qter. A survey of abnormalities of chromosome No. 1 in this series and in other patients with CML previously reported show, in all patients, a relative increase or decrease of genetic material of two specific regions: 1q32–1q42 and 1p36–1pter

Chromatid recommensuration after segmental duplication

<p>Abstract</p> <p>Background</p> <p>Midsegment duplication (dup) of chromatid arms may be symmetric or asymmetric. It can be argued that every dup should yield a discommensured RC with (a) loss of at least one duplicated unit to the template counterpart and; (b) deletion of all sections of the replicating chromatid arm that are distal to both the gap left by the duplicating process and the segment closest to the centromere.</p> <p>Hypothesis</p> <p>Mechanisms capable of recommensuring the stack of chromatids after topological shifts of duplicated units (dups) are discussed. The mechanics might fail in few cases, which are discussed in terms of statistics and scalability.</p> <p>Conclusion</p> <p>The dynamics of the highly non-linear processes discussed here may be relevant to duplications of smaller (epsilon) subunits such as telomeric units within malignant genomes.</p

EML4–ALK fusion transcript is not found in gastrointestinal and breast cancers

Fusion genes have been identified as chromosomal rearrangements in certain cancers, such as leukaemia, lymphoma, and sarcoma. The EML4–ALK (EML4: echinoderm microtubule-associated-protein-like 4; ALK: anaplastic lymphoma kinase) fusion gene has been identified as an oncogene in non-small-cell lung cancer (NSCLC). This study examined the presence of this fusion transcript in gastrointestinal and breast cancers. We evaluated the expression of the EML4–ALK transcript in 104 lung cancer cases and in 645 gastrointestinal and breast cancer samples. Only one of the lung cancer samples tested positive for the EML4–ALK fusion transcript, whereas none were detected in 555 gastrointestinal and 90 breast cancer cases. Our data suggest that the EML4–ALK fusion transcript is not present in gastrointestinal or breast cancers and is specific to NSCLC

Measurement of Th1/Th2 serum cytokines by flow cytometry in classical Hodgkin lymphoma

O linfoma de Hodgkin clássico (LHC) é uma neoplasia com distúrbio na produção de citocinas. Estudos demonstram que o padrão anormal das citocinas no linfonodo acometido pela lesão contribui não somente com a proliferação das células malignas H-RS, como também com o característico infiltrado hiper-reativo que compõe o tecido no LHC. Esta disfunção pode ser observada tanto no quadro clínico dos pacientes, como nas características histopatológicas: sintomas B, deficiência na resposta imune celular, bandas de colágeno e eosinofilia. As concentrações séricas das citocinas Th1 (IL-2, TNF, INF-&#947;) e Th2 (IL-4, IL-5, IL-10) foram estudadas em 45 pacientes com LHC, ao diagnóstico, e em 34 doadores saudáveis, por citometria de fluxo (CBA - cytometric beads array). Houve aumento das concentrações das citocinas TNF (p<0,01), INF-&#947; (p<0,01), IL-4 (p=0,01), IL-5 (p<0,01) e IL-10 (p<0,01) dos pacientes quando comparados com o grupo controle. Não foi evidenciada diferença em relação a IL-2. Ao correlacionarmos as concentrações das citocinas Th1/Th2 com as variáveis clínico-laboratoriais dos pacientes, observou-se que níveis elevados da IL-10 (Th2) estão correlacionados com as variáveis que implicam em pior prognóstico: estádios III/IV (p=0,01), presença de sintomas B (p=0,04), hemoglobina < 10,5g/dL (p=0+,01), linfócitos <600 mm³ (p=0,01) e, de acordo com o IPI, os pacientes de alto risco (p=0,01). Por outro lado, níveis séricos elevados da IL-2 (Th1) foram encontrados em estádio I/II, quando comparados com III/IV (p=0,03), o que indica que a IL-2 diminui com a progressão da doença. Os resultados sugerem que a IL-10 possa estar regulando negativamente a resposta imune citotóxica (Th1) pela inibição da IL-2. Há uma possível associação entre progressão da doença e níveis elevados da IL-10. Esse estudo evidenciou que a utilização do CBA é factível na detecção das citocinas, e que as alterações encontradas podem estar envolvidas na biologia do LHC.Classical Hodgkin lymphoma (CHL) is a malignancy with an abnormal or unbalanced secretion/production of cytokines, which might support the growth of H-RS cells, their surrounding reactive bystander cells and may be responsible for the typical clinical and histopathologic features of CHL: systemic B symptoms, an apparent defect in cell-mediated immune response, tumor fibrosis and eosinophilic infiltrate. Serum concentrations of IL-2, IL-4, IL5, IL-10, TNF and IFN-&#947; (Th1/Th2) were measured in 45 patients at diagnosis of classical Hodgkin lymphoma and in 34 healthy controls by cytometric beads array (CBA). Levels of TNF (p<0.01), INF-&#947;(p<0.01), IL-4 (p=0.01), IL-5 (p<0.01) e IL-10 (p<0.01) were significantly higher in patients compared to the control group. No difference was observed for IL-2 between the two groups. On correlating Th1/Th2 cytokine concentrations with clinical risk factors, elevated IL-10 (Th2) levels are associated with variables that suggest worse prognoses including III/IV stage (p=0.01), B-symptoms (p=0.04), hemoglobin < 10.5g/dL (p=0.01), lymphocytes < 600/mm³ (p=0.01) and according to the seven-factored international prognostic score (IPI), a subset of patients with a particularly high risk of failure (p=0.01). Furthermore, the serum levels of IL-2 (Th1) were significantly higher in a group of I/II stage patients compared to III/IV patients (p=0.03) which implies that, the levels of IL-2 might decrease with disease progression. The elevated IL-10 levels in a subset of patients with poor clinical risk factors might down regulate a Th1 immune response by inhibiting IL-2 production causing survival disadvantage by suppression of the cytotoxic immune response against the tumor. This suggests an association between progression of CHL and higher levels of the IL-10 cytokine. This study showed that measurement of serum cytokines using the CBA methodology is highly reproducible, and that changes in concentrations seem to be involved in the biology of this diseas

Poly‐aneuploid cancer cells promote evolvability, generating lethal cancer

Cancer cells utilize the forces of natural selection to evolve evolvability allowing a constant supply of heritable variation that permits a cancer species to evolutionary track changing hazards and opportunities. Over time, the dynamic tumor ecosystem is exposed to extreme, catastrophic changes in the conditions of the tumor—natural (e.g., loss of blood supply) or imposed (therapeutic). While the nature of these catastrophes may be varied or unique, their common property may be to doom the current cancer phenotype unless it evolves rapidly. Poly‐aneuploid cancer cells (PACCs) may serve as efficient sources of heritable variation that allows cancer cells to evolve rapidly, speciate, evolutionarily track their environment, and most critically for patient outcome and survival, permit evolutionary rescue, therapy resistance, and metastasis. As a conditional evolutionary strategy, they permit the cancer cells to accelerate evolution under stress and slow down the generation of heritable variation when conditions are more favorable or when the cancer cells are closer to an evolutionary optimum. We hypothesize that they play a critical and outsized role in lethality by their increased capacity for invasion and motility, for enduring novel and stressful environments, and for generating heritable variation that can be dispensed to their 2N+ aneuploid progeny that make up the bulk of cancer cells within a tumor, providing population rescue in response to therapeutic stress. Targeting PACCs is essential to cancer therapy and patient cure—without the eradication of the resilient PACCs, cancer will recur in treated patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156440/2/eva12929_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156440/1/eva12929.pd