A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

Inversiones cromosómicas (anomalías estructurales poco frecuentes) asociadas a fenotipo normal, dudoso y patológico / Chromosomal inversions (Slight structural anomalies) associated to normal, doubtfull and pathological phenotypes

Las inversiones son reordenamientos intracromosómicos originados por dos rupturas en un cromosoma seguidas de la reinserción del fragmento rotado en 180º. Dependiendo si involucra o no al centrómero pueden ser pericén tricas o paracéntricas. La incidencia es 0.09 a 0.49/1.000. Las inversiones son rearreglos estructurales aparentemente equilibrados, por lo que la mayoría de los individuos portadores tienen fenotipos normales y una minoría tienen fenotipos patológicos (probablemente por alteración en la secuencia de genes o variación en la función de éstos por efectos de cambio de posición). Se presentan tres casos de inversiones detectas por la técnica de Bandeo G y confirmadas por Hibridación In Situ Fluorescente (FISH). Caso 1: INVERSION PARACENTRICA FAMILIAR DEL CROMOSOMA 13 ASOCIADA A RETRASO MENTAL Y DISMORFIAS. El exhaustivo análisis del árbol genealógico y el estudio cromosómico al mayor número posible de individuos permitió confirmar la asociación inversión/fenotipo patológico en este grupo familiar. 13 de 17 miembros son portadores de inv(13)(q31q32)inh.ish inv(13)(q31q32) (wcp13+). Caso 2: INVERSION PARACENTRICA DEL CROMOSOMA 6 DE NOVO EN RECIEN NACIDO CON RETRASO MADURATIVO GLOBAL Y RETRASO DEL CRECIMIENTO INTRAUTERINO. En este caso no es posible adjudicar que, el fenotipo afectado se deba a la inversión. Cariotipo: 46,XY,add(6)(q21)dn.ish inv(6)(q21q27)(wcp6+). Caso 3: INVERSION PERICENTRICA DEL CROMOSOMA 12 EN OVODONANTE. Dicha inversión no parece tener efecto sobre el fenotipo, ya que es una paciente con coeficiente intelectual normal y no presenta malformaciones congénitas. Cariotipo: 46,XX,inv(12)(p12q14).ish inv(12) (p12q14)(wcp12+). Este reporte de casos muestra los tres fenotipos posibles de una inversión: patológico, dudoso y normal. Es el primer reporte de una inv(13) que confiera fenotipo patológico.

The inversions are intrachromosomal rearrangements which occur when a single chromosome undergoes two breaks and the region between it's rotates 180 degrees before rejoining. Depending on whether or not it include the centromere, they can be pericentric or paracentric. The incidence is 0.09 to 0.49/1,000. The inversions are apparently balanced structural rearrangements, so the most of the carrier individuals show normal phenotypes and a minority have pathological phenotypes (probably due to variation in their function due to changes in position). Three cases of inversions detected by the G Banding technique and confirmed by Fluorescence In Situ Hybridization (FISH) are presented. Case 1: FAMILIAL PARACENTRIC INVERSION OF CHROMOSOME 13 ASSOCIATED WITH MENTAL RETARDATION AND DISMORPHIA. The exhaustive analysis of the pedigree and the chromosomal study to the greatest possible number of individuals confirmed the inversion/pathological phenotype association in this family group. 13 of 17 members are carriers of inv(13)(q31q32)inh.ish inv(13)(q31q32)(wcp13+). Case 2: PARACENTRAL INVERSION DE NOVO OF CHROMOSOME 6 IN NEWBORN WITH GLOBAL MATURITY DELAY AND DELAY OF INTRAUTERINE GROWTH. In this case it is not possible to adjudge that, the affected phenotype is due to the inversion. Karyotype: 46,XY,add(6)(q21)dn.ish inv(6)(q21q27)(wcp6+). Case 3: PERICENTRIC INVERSION OF CHROMOSOME 12 IN OVODONANT. This inversion does not seem to have an effect on the phenotype, since it is a patient with normal IQ and does not present congenital malformations. Karyotype: 46,XX,inv(12)(p12q14).ish inv(12) (p12q14)(wcp12+). This case report shows the three possible phenotypes of an inversion: pathological, questionable and normal. It is the first report of an inv(13) that confers pathological phenotype. Key words: chromosomal inversion, G Banding, phenotype, structural rearrangement, fluorescence in situ hybridization.

Reporte de caso por infección de virus Influenza A H1N1: hallazgos de autopsia / Case report of Influenza virus H1N1 infection: autopsy findings

La influenza continúa siendo una causa importante de muerte en las Américas; en nuestro país al igual que en otros países del continente, hay circulación viral sostenida del virus Influenza A H1N1pdm09, este reporte describe los hallazgos histopatológicos más relevantes, encontrados en femenina de 32 años de edad, con antecedentes de anemia drepanocítica; que falleció tres días después de inicio de síntomas respiratorios. La autopsia estableció como causa de muerte neumonía, daño alveolar difuso (DAD), edema, hemorragia, membranas hialinas y colonias bacterianas secundarias a infección por virus Influenza AH1N1pdm09. Este reporte destaca la importancia que el médico forense realice una labor integrativa, de los hallazgos macro y microscópicos y exámenes complementarios de la autopsia en el contexto epidemiológico y clínico en el que se dan los decesos...(AU)

Minimal residual disease detection in Tunisian B-acute lymphoblastic leukemia based on immunoglobulin gene rearrangements

IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL). Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD) after induction chemotherapy. Seventeen consecutive newly diagnosed B-ALL patients were investigated by multiplex PCR assay and real time quantitative PCR according to BIOMED 2 conditions. The vast majority of clonal VH-JH rearrangements included VH3 gene. For IGK deletion, clonal VK1f/6-Kde recombinations were mainly identified. These rearrangements were quantified to follow-up seven B-ALL after induction using patient-specific ASO. Four patients had an undetectable level of MRD with a sensitivity of up to 10-5. This molecular approach allowed identification of prognosis risk group and adequate therapeutic decision. The IGK-Kde and IGH gene rearrangements might be used for diagnosis and MRD monitoring of B-ALL, introduced for the first time in Tunisian laboratories.

Immunoglobulin heavy chain gene rearrangement in non B-cell haematological malignancies / Reordenamiento del gen de la cadena pesada de inmunoglobulina en las neoplasias hematológicas de linfocitos no B

PURPOSE: Clonality detection through amplifying immunoglobulin heavy chain (IGH) gene rearrangements by polymerase chain reaction (PCR) is a useful tool in diagnosis of various B-lymphoid malignancies. Immunoglobulin heavy chain gene rearrangement can be an optimal target for clonality detection in B-lymphoid malignancies. In the present study, we evaluated the presence of IGH gene rearrangement in non B-cell haemato-oncologypatients including T-cell acute lymphoblastic leukaemia (T-ALL), acute myeloblastic leukaemia (AML) and biphenotypic leukaemia. METHODS: We studied 18 cases of haematological malignancies which comprised five patients with TALL, 12 patients with AML and one with biphenotypic leukaemia. RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement. CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.

OBJETIVO: La detección de la clonalidad mediante amplificación de los reordenamientos del gen de la cadena pesada (IGH) de inmunoglobulina por reacción en cadena de la polimerasa (RCP) es una herramienta útil en el diagnóstico de varios tumores malignos linfoides de células B. El reordenamiento del gen de la cadena pesada de inmunoglobulina puede ser un objetivo óptimo de la detección de la clonalidad en tumores malignos linfoides de células B. En el presente estudio, se evaluó la presencia de reordenamiento del gen IGH en pacientes de hemato-oncología de células no B, incluyendo la leucemia linfoblástica aguda de células T (LLA-T), leucemia mieloblástica aguda (LMA), y leucemia bifenotípica. MÉTODOS: Se estudiaron 18 casos de neoplasias malignas hematológicas que abarcaron cinco pacientes con (LLA-T), 12pacientes con AML y uno con leucemia bifenotípica. CONCLUSIÓN: Reordenamiento del gen de la inmunoglobulina que ocurre en casi todas las neoplasias malignas hematológicas del linaje de las células B, también se presenta en una proporción muy pequeña de células T o las neoplasias mieloides.

Detecção do rearranjo da proteína BCL2/JH em carcinomas epidermoides de boca e faringe / Detection of protein BCL2/JH rearrangement in epidermoid carcinomas of mouth and pharynx

Introdução: A proteína BCL2 encontrada na membrana mitocondrial interna, regula a apoptose inibindo a morte celular programada. A translocação (14;18), detectada em 70 a 85% dos linfomas foliculares, leva a superexpressão da proteína BCL2, pela justaposição do gene BCL2 ao segmento JH do gene da cadeia pesada da imunoglobulina. Porém, os achados da expressão da BCL2 em carcinoma de cabeça e pescoço são contraditórios. Objetivo: Investigar a presença da translocação (14;18) do gene BCL2 em carcinomas de cabeça e pescoço. Método: Foram examinadas 16 amostras de DNA, sendo 13 de carcinomas de células escamosas (CCE) e 3 de epidermoide (CE), por meio da reação em cadeia da polimerase (PCR). Resultados: O rearranjo BCL2/JH foi encontrado em 2 (15%) dos 13 casos de CCE e em nenhum dos 3 casos de CE. A média de frequência de moléculas com rearranjo foi de 46,44 x 107. Não foi observada associação entre a presença de rearranjo e a exposição ao tabaco e álcool (p=0,6545). Conclusão: Diferente dos resultados encontrados em linfomas foliculares a presença da translocação (14;18) em carcinomas de cabeça e pescoço não é comum e, quando ocorre, pode ser uma mutação ocasional não associada a exposição ao tabaco e álcool.

Introduction: The BCL2 protein found in the internal mothocondrial membrana regulates the apoptosis preventing the programmed cell death. The translocation (14:18), detected in 70 to 85% of the follicular lymphoma, lead the super expression of BCL2 protein, by juxtaposition of BCL2 gene to the JH segment of the immunoglobulins' heavy chain gene. However, the found of the BCL2 expression in head and neck carcinoma are contradictious. Objective: To investigate the presence of the translocation (14:18) of the BCL2 gene in head and neck carcinoma. Method: Sixteen DNA samplers were examinated being 13 of squamous cells carcinoma (SCC) and 3 of epidermoid (CE), y means of chain reaction of the polymerase (PCR). Results: The BCL2/JH rearrangement in 2 (15%) of the CCE 13 cases and in none of the 3 cases of CE. The average of the frequency of molecules with rearrangement was 46,44x107. Was not observed association between the rearrangement presence and the exhibition to tobacco and alcohol (p=0, 6545). Conclusion: Different from the results found in follicular lymphoma, the presence of the translocation (14; 18) in head and neck carcinomas is not common and, when it occurs, it can be an occasional mutation not associated to exhibition to the tobacco and alcohol.

Clinical prognosis in BRAF-mutated PTC

BRAF mutation has recently emerged as a potential prognostic marker for papillary thyroid carcinoma (PTC) due to several studies suggesting that it may condition the development of tumors with aggressive behavior. A study of the phenotypes of thyroid follicular cell lines and transgenic mice characterized by targeted expression of BRAF mutation indicates that, at variance with RET/PTC rearrangement, it induces or facilitates genomic instability and higher invasiveness and eventually deeper tumor de-differentiation and more significant suppression of apoptosis. An analysis of differential gene expression of PTCs harboring BRAF mutation versus PTCs characterized by other genetic alterations shows an important impairment of the expression of genes related to intra-thyroidal iodine metabolism machinery, up-regulation of Glut-1 mRNA, methylation-induced gene silencing of tumor suppressor genes and up-regulation of pro-angiogenetic proteins such as VEGF. Correlation of BRAF mutation with PTC clinico-pathological features yields controversial results, with several studies showing the association with unfavourable clinico-pathological qualities, while others do not confirm the findings. This review will summarize the studies in favor of or in contrast with a role of BRAF mutation as a prognostic marker in PTC. We will also indicate what information we still need in order to routinely introduce this indicator in clinical practice.

Mutações no BRAF surgiram recentemente como potenciais marcadores prognósticos do carcinoma papílifero de tiróide (CPT) graças a vários estudos que sugerem que ele possa condicionar o desenvolvimento de tumores com comportamento agressivo. Um estudo do fenótipo das células de linhagem folicular de tiróide em camundongos transgênicos caracterizados pela expressão direcionada de mutações BRAF, indicam, à semelhança dos rearranjos RET/PTC, que ele induz ou facilita a instabilidade genômica, a alta invasividade e, por fim, uma profunda desdiferenciação tumoral com supressão mais significativa da apoptose. Uma análise da expressão gênica diferencial do CPT associado com mutações BRAF versus o CPT caracterizado por outras alterações gênicas mostra uma redução importante da expressão dos genes relacionados com a maquinaria do metabolismo do iodo intratiroideano, aumento da regulação do mRNA do Glut-1, silenciamento gênico induzido por metilação dos genes supressores tumorais e aumento da regulação das proteínas pró-angiogênicas, como a VEGF. A correlação da mutação BRAF com os achados clínico-patológicos do CPT mostra resultados controversos, com vários estudos indicando associação com parâmetros clínico-patológicos desfavoráveis e outros não confirmando esses achados. Esta revisão sumariza os estudos a favor ou não do papel da mutação BRAF como um marcador prognóstico no CPT. Indicaremos, também, quais informações são ainda necessárias para a introdução rotineira deste indicador na prática clínica.

Molecular genetics of papillary thyroid carcinoma: great expectations...

Papillary thyroid carcinoma (PTC) is the most prevalent type of endocrine cancer and, in recent epidemiological surveys, one of the types of human cancer whose incidence is growing. Despite the favourable outcome and long survival rates of most patients, some tumours display an aggressive behaviour and may progress to the highly aggressive and lethal, anaplastic thyroid carcinoma. In recent years, several progresses have been made on the molecular characterization of PTC, in general, and in the genetic alterations underlying the histotype diversity of this type of cancer, in particular. This holds true regarding alterations on nuclear DNA as well as mitochondrial DNA. In this review we have summarized the most recent findings in the genetic characterization of PTC, giving a particular emphasis to the genotype-phenotype associations, the prognosis implications, and the diagnostic and therapeutic value of the newly identified genetic markers.

O carcinoma papilífero de tireóide (CPT) é o tipo mais prevalente de câncer endócrino e, em pesquisas epidemiológicas recentes, um dos tipos de câncer humano cuja incidência vêm crescendo. A despeito do prognóstico favorável e da longa taxa de sobrevivência da maioria dos pacientes, alguns tumores mostram um comportamento agressivo e podem progredir para o altamente agressivo e letal carcinoma anaplásico de tireóide. Recentemente, vários progressos foram feitos quanto à caracterização molecular do CPT, em general, e às alterações genéticas subjacentes à diversidade histológica desse tipo de câncer, em particular, particularmente com respeito às alterações dos DNAs nuclear e mitocondrial. Nesta revisão, nós sumarizamos os achados mais recentes da caracterização genética do CPT, dando ênfase particular às associações genótipo-fenótipo, às implicações prognósticas e ao valor diagnóstico e terapêutico dos marcadores genéticos recentemente identificados.

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of ú0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

Patogênese dos tumores diferenciados da tiróide (papilífero e folicular) / Pathogenesis of differentiated thyroid cancer (papillary and follicular)

Os carcinomas diferenciados da tiróide, o papilífero (PTC) e o folicular (FTC) são as neoplasias endócrinas mais comuns. Descobertas recentes esclareceram diversos aspectos de sua patogênese, analisados nesta revisão. No PTC, uma única mutação no gene BRAF (o gene da Raf quinase tipo B) (V600E) é responsável pela doença em 40-50% dos pacientes, especialmente os mais velhos e os que apresentam subtipos histológicos mais agressivos. Tendo em vista esses fatores prognósticos da mutação BRAF, o uso de sua pesquisa no material proveniente do exame citológico de tiróide pode ser útil para fins de diagnóstico e conduta. A outra causa freqüente de PTC são os rearranjos RET/PTC, decorrentes da quebra e fusão do domínio TK intra-celular de RET com fragmentos 5’ de diversos genes, resultando num gene quimérico que produz uma proteína que apresenta atividade constitutiva de uma tirosina quinase de RET, presentes em 20-30% dos pacientes, especialmente os mais jovens ou que receberam radiação. Já a patogênese do FTC é menos compreendida. Descreve-se a participação do gene decorrente da fusão entre PAX8 e PPARg (peroxisome proliferator-activated receptor g) em 30-50% dos pacientes com este tumor; entretanto, esta fusão pode ocorrer também em adenomas foliculares. Desta forma, ainda não há evidência completa de que PAX8-PPARg seja a causa do FTC. Outro achado no FTC são as mutações no gene RAS; quando ocorrem mutações do RAS não acontece o rearranjo PAX8-PPARg. Outra possível causa de FTC é a perda ou expressão exagerada de uma série de genes, alguns demonstrados por técnicas de expressão diferencial de genes, como TRg, PTEN, PKAR1A, DDIT3, ARG2, ITM1 e C1orf24.

Rearreglos de genes de cadenas pesadas de las inmunoglobulinas en las gammapatias monoclonales / Immunoglobulin heavy chain gene rearrangements in the monoclonal gammopathies

Las neoplasias de células plasmáticas resultan de la expansión de un clon de células B que secreta inmunoglobulinas, conocido como componente monoclonal o componente M. Las neoplasias malignas incluyen al mieloma múltiple y la macroglobulinemia de Waldenström, y la condición premaligna comprende las gammapatías monoclonales de significado incierto (MGUS). El MGUS presenta un componente monoclonal sin evidencia de mieloma múltiple, macroglobulinemia de Waldenström, amiloidosis primaria u otros desórdenes. El diagnóstico se basa en la combinación de características patológicas, radiológicas y clínicas. Aproximadamente el 25% de las gammapatías monoclonales de significado incierto desarrollarán mieloma múltiple, amiloidosis sistémica, macroglobulinemia o enfermedades linfoproliferativas malignas, indicando que sería una condición premielomatosa. El objetivo del presente trabajo es establecer la utilidad clínica de la inmunofenotipificación por citometría de flujo (CF) y la detección de clonalidad por biología molecular. Se estudiaron 32 pacientes, siete con diagnóstico de mieloma múltiple y veinticinco con gammapatía monoclonal em estudio, los cuales fueron divididos en cuatro grupos basados en los datos clínicos y los resultados de CF. Em el grupo de pacientes con CF no diagnóstica, se realizó la detección de los rearreglos de los genes de las cadenas pesadas de las inmunoglobulinas mediante reacción en cadena de la polimerasa (PCR), detectándose monoclonalidad en el 59% de los casos. El estudio de los rearreglos de los genes de las cadenas pesadas de las IgH mediante PCR incrementa la sensibilidad de detección de monoclonalidad.

Use of nonradioactive labeling to detect large gene rearrangements in 21-hydroxylase deficiency

OBJETIVO: Padronizar a técnica de Southern blotting usando hibridização com material não radioativo para detectar grandes rearranjos no gene CYP21A2 em uma amostra da população brasileira com hiperplasia adrenal congênita. MÉTODO: Foram estudados 42 pacientes, 2 dos quais aparentados, totalizando 80 alelos não relacionados. As amostras de DNA foram obtidas de sangue periférico, digeridas com enzima de restrição Taq I, realizado Southern blotting e hibridizadas com sonda marcada com biotina. RESULTADOS: O método se mostrou eficaz, com resultados similares aos encontrados ao utilizar a metodologia com material radioativo. Foram encontradas 2,5% de deleção do CYP21A2, 8,8% de grandes conversões, 3,8% de deleção do CYP21A1P e 6,3% de duplicação do CYP21A1P. Estas freqüências foram similares às encontradas em nosso estudo prévio, onde um número significante de casos foi estudado. Um bom padrão de hibridização foi alcançado utilizando menor quantidade de DNA (5mg) e a emissão de sinais foi observada entre 5 minutos e 1 hora de exposição. CONCLUSÕES: Padronizamos uma técnica de Southern blotting/ hibridização com material não radioativo (biotina) para a pesquisa de grandes rearranjos no gene CYP21A2 com bons resultados. Apesar de ser mais trabalhoso, este método é mais rápido, utiliza menores quantidades de DNA e, principalmente, evita problemas com o uso de radioatividade.

Human mutations and their detection by gene and linkage analysis, allele sharing and association methods

It has been 20 years since DNA analysis was first used in the detection of sickle-cell anaemia. Here, techniques for detecting human mutations are reviewed. We describe direct detection of mutations using restriction enzyme analysis and polymerase chain reaction amplification to detect gene deletions, rearrangements and point mutations. Indirect detection of mutations include the use of DNA polymorphisms in linkage analysis

Apparent absence of bcl-2 rearrangement in ten Saudi follicular lymphomas: a preliminary report

Specific chromosomal translocations are often found to be associated with distinct types of human neoplasms. The t [14; 18] is considered to be a cytogenetic hallmark of the follicular lymphomas found mostly in American patients. This chromosomal translocation occurs through a 3 untranslated region [either major breakpoint region [mbr] or minor cluster region [mcr]] of the bcl-2 proto-oncogene in chromosome 18 and the J H region of the immunoglobulin [Ig] gene in chromosome 14. In the present study, the polymerase chain reaction [PCR] was used to detect a fusion DNA fragment generated from bcl-2/ J H rearrangement either through mbr or mcr in 10 follicular lymphomas in Saudi Arab patients. Surprisingly, none of these cases showed any evidence of bcl-2 gene rearrangement through mbr or mcr. The absence of usual bcl-2/ J H recombination in Saudi follicular lymphomas is intriguing and may suggest that the occurrence and mode of bcl-2 gene rearrangement in this lymphoma varies in different patient populations

Molecular cytogenetics of human cancer.

Cancer may arise from the genetic transformation of a single precursor cell, which proliferates to form a clone. Chromosomal abnormalities are associated with many types of tumours. Some of the chromosomal rearrangements such as translocation, deletion and insertion involve breakage of chromosomes close to known oncogenes. The close linkage between the chromosomal changes, the gene modifications and consequently altered protein function seen in malignant cells suggest that cancer is a genetic disease. Analysis of chromosomal abnormalities and oncogene amplifications in malignant cells have been found to be related to their malignant potential and hence may be utilized in the clinical management of patients with cancer.