DBD-FISH Using Specific Chromosomal Region Probes for the Study of Cervical Carcinoma Progression.

Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.

Chromatin Dispersion Test to Asses DNA Damage in Cervical Epithelial Cells.

The chromatin dispersion test (CDT) is based on the removal of nuclear proteins under the assumption that cells with fragmented DNA produce a typical halo of circular DNA loops, which is absent in cells with non-fragmented DNA. This method represents a simple, rapid, accurate, highly reproducible, and inexpensive technique to assess nuclear DNA damage in somatic cells. The visualization of DNA damage and the capacity of the test to provide a threshold value to discriminate between high and low levels of cervical lesions would aid in determining the malignant transformation. All of these advantages associated with the CDT protocol could promote this technique as a tool for the quick and reliable diagnosis of cervical epithelial disorders, even at primary-care centers.

Thermal stress induces pyknosis in pigeon erythrocytes: digital image analysis.

Pyknosis or hypercondensation of chromatin is informative in the understanding of nucleosomal packing in translationally inactive chromatin and in the compression of cell death. However, mechanisms that result in the formation of avian erythrocytes with variant nuclear morphology are poorly understood.Purpose: In this work, we evaluated pyknosis in pigeon erythrocytes treated with thermal stress using Digital Image Analysis (DIA).Materials and methods: Pigeon erythrocytes were treated at thermal stress (33 °C, 43 °C, and 53 °C), and nuclear modifications were analyzed by DIA.Results: Our results showed that thermal stress induced DNA condensation. Based on DNA fluorescent staining and compaction, four subclasses with progressively more pyknotic nuclei each could be distinguished. Alkaline comet assay showed that the presence of pyknotic nuclei was associated with the DNA fragmentation typical of apoptosis. DIA analysis showed a decrease of nuclear area and a significant increase of fluorescence intensity with respect to non-pyknotic nucleus. Additionally we observed nuclear dissolution events associated with swell and loose membrane integrity.Conclusion: These findings can contribute to the evaluation of health and metabolic status in diagnostic cytology, especially in neoplastic conditions and infection by microorganisms.

Quick assessment of DNA damage in cervical epithelial cells using a chromatin dispersion test.

PURPOSE: This study was aimed to quantify genomic DNA breakages in the cervical epithelium cells of patients diagnosed with different grades of cervical lesions using a quick test based on chromatin dispersion after controlled protein depletion. The association between the progressive stages of cervical dysplasia and the levels of DNA damage, taking into account the presence of papillomavirus human (HPV) infection, was investigated. METHODS: A hospital-based unmatched case-control study was conducted during 2018 with a sample of 78 women grouped according to histological diagnosis as follows: 23 women with low grade-squamous intraepithelial lesion (LG-SIL), 34 women with high grade- squamous intraepithelial lesion (HG-SIL), and three women with cervical carcinoma (CC). In parallel, 15 women without cervical lesions were included as a Control cohort. DNA damage levels in cervical epithelial cells were assessed using the chromatin dispersion test (CDT) and controlled in parallel with DNA breakage detection coupled with florescent in situ hybridization (DBD‒FISH) using whole genomic DNA probes. RESULTS: CDT produces different morphotypes in the cervical epithelium that can be associated with the level of DNA breakage revealed with DBD‒FISH. A significant increase of DNA damage was correlated with the histological progression of the patients and human papillomavirus (HPV) infection. CONCLUSION: The CDT is a simple, accurate and inexpensive morphological bioassay to identify different levels DNA damage that can be associated with the level of abnormal cells present in the cervical epithelium in patients who commonly present HPV infection.

DBD-FISH, an effective marker for detecting genotoxicity in buccal mucosa exfoliated cells of patients with oral cancer.

Oral squamous cell carcinoma (OSCC) is characterized by increased genetic instability as an essential variable of event of neoplastic transformation. The aim of this study was to evaluate genomic instability in exfoliated cells from the buccal mucosa of patients with OSCC vs. the control group, using DNA Breakage Detection/Fluorescence In Situ hybridization (DBD-FISH). Exfoliated cells from the buccal mucosa were obtained from 38 patients with oral cancer (case group) and from 10 individuals without oral lesions (control group). DNA damage was evaluated by DBD-FISH using the whole-genome DNA probe and digital imaging analysis. Collaterally, HPV infection was determined utilizing the INNO-LiPA HPV kit. Patients with OSCC showed an increase in the hybridization signal five times more intense than that of the baseline level of DNA damage detected in control individuals. The best cutoff value for predicting oral squamous cell carcinoma was 67.46, and an Odds Ratio (OR) value of 87. HPV detection analysis revealed than one patient with OSCC (2.6%) was positive for HPV. All controls were negative HPV. In conclusion, DBD-FISH permitted the clear visualization of level high of DNA damage in the buccal epithelial cells of patients with OSSC respect to control group. Chromosome instability in oral mucosa may be an individual marker of malignant transformation in OSCC.

Leptin receptor expression during the progression of endometrial carcinoma is correlated with estrogen and progesterone receptors.

INTRODUCTION: The hormone leptin, which is produced in the adipose tissue, may influence tumorigenesis directly via its receptor (Ob-R). Thus, a role for Ob-R in endometrial carcinogenesis has been proposed. However, most studies neither included samples of the entire histological progression of endometrial carcinoma nor examined Ob-R jointly with the estrogen and progesterone receptors (ER and PR, respectively). MATERIAL AND METHODS: To determine the fluctuations of Ob-R, ER, and PR during the histological progression of endometrial carcinoma, we assessed their expression via immunohistochemistry (IHC) in six histological types of endometrium (proliferative, secretory, nonatypical and atypical hyperplasia, and endometrioid and nonendometrioid endometrial carcinoma), in which we performed histopathological and digital scoring for the quantification of receptors. RESULTS: We found that Ob-R expression was positively correlated with that of ER and PR (r = 1, p < 0.001; r = 0.943, p < 0.005, respectively), and there was a significant difference in Ob-R expression among proliferative normal endometrium, hyperplasias, and carcinomas, according to their relative digitally scored Ob-R expression (p < 0.001). In addition, we observed that Ob-R expression in the secretory endometrium was more similar to that of carcinomas than to its proliferative counterpart. CONCLUSIONS: These results indicate that Ob-R expression fluctuates during endometrial carcinogenesis in correlation with ER and PR, suggesting that Ob-R expression in vivo is highly dependent on estrogen and progesterone activities in the endometrium and on its ER and PR status, as suggested previously by in vitro studies.

DNA damage in acute myeloid leukemia patients of Northern Mexico.

The purpose of this study was to evaluate DNA damage in the whole genome of peripheral blood leukocytes from patients with acute myeloid leukemia (AML) compared with a control group using DNA breakage detection-fluorescent in situ hybridization (DBD-FISH). Our results suggest that the DNA damage detected in patients with newly diagnosed AML was similar to that observed for the controls; this might be explained by the stimulation of a repair pathway by the pathogenesis itself. These findings indicate that inhibiting the repair pathway could be proposed to enhance the efficacy of chemotherapy.

Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma.

Evaluation of environmental genotoxicity by comet assay in Columba livia.

The concentrations of recognized or suspected genotoxic and carcinogenic agents found in the air of large cities and, in particular, developing countries, have raised concerns about the potential for chronic health effects in the populations exposed to them. The biomonitoring of environmental genotoxicity requires the selection of representative organisms as "sentinels," as well as the development of suitable and sensitive assays, such as those aimed at assessing DNA damage. The aim of this study was to evaluate DNA damage levels in erythrocytes from Columba livia living in the metropolitan area of Monterrey, Mexico, compared with control animals via comet assay, and to confirm the results via Micronuclei test (MN) and DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). Our results showed a significant increase in DNA migration in animals from the area assayed compared with that observed in control animals sampled in non-contaminated areas. These results were confirmed by MN test and DBD-FISH. In conclusion, these observations confirm that the examination of erythrocytes from Columba livia via alkaline comet assay provides a sensitive and reliable end point for the detection of environmental genotoxicants.

Use of DBD-FISH for the study of cervical cancer progression.

DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) is a procedure to detect and quantify DNA breaks in single cells, either in the whole genome or within specific DNA sequences. This methodology combines microgel embedding of cells and DNA unwinding procedures with the power of FISH coupled to digital image analysis. Cells trapped within an agarose matrix are lysed and immersed in an alkaline unwinding solution that produces single-stranded DNA motifs beginning at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with fluorescently labeled DNA probes. The amount of hybridized probe at a target sequence correlates with the amount of single-stranded DNA generated during the unwinding step, which is in turn proportional to the degree of local DNA breakage. A general view of the technique is provided, emphasizing its versatility for evaluating the association between DNA damage and progressive stages of cervical neoplasia.

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH).

We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

Evaluation of DNA single and double strand breaks in women with cervical neoplasia based on alkaline and neutral comet assay techniques.

A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r(2) = 0.99, P = 0.03, and r(2) = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb.

Molecular detection of cryptic Y-chromosomal material in patients with Turner syndrome.

A systematic search for a hidden Y-chromosome mosaicism, in Turner syndrome (TS) patients is justified by the evaluation of the risk of development of germ cell tumors. In this study, we analyzed cryptic Y-chromosome derivatives by polymerase chain reaction (PCR) coupled with fluorescence in situ hybridization (FISH) using Y-specific sequences in patients with TS, and validated this methodology. Unrelated patients with TS (n=32) of Mexican mestizo ethnic origin were diagnosed using cytogenetic analysis. Clinical assessment, endocrine evaluation, karyotyping, FISH and PCR analysis of the Y-chromosomal loci were performed. We found that 9.4% (3 out of 32) patients with TS had Y-chromosome material. Two patients showed Y-chromosome by conventional cytogenetics. One patient had no Y-chromosome by initial karyotyping (45, X) but was positive by lymphocyte PCR DNA analysis of the Y-sequence-specific sex-determining region Y (SRY) gene. Our results suggest that the detection of the Y-chromosome material using sensitive methods, such as PCR coupled with FISH, should be carried out in all patients with TS and should not be limited to TS patients with cytogenetically identifiable Y-chromosome and/or virilization.

Monosomy of chromosome 8 could be considered as a primary preneoplastic event in breast cancer: A preliminary study.

This pilot study analyzed and compared the presence of chromosome 8 aneusomy in Mexican women with breast cancer and adjacent, intraductal, proliferative lesions. To determine the chromosome 8 copy number, we performed fluorescence in situ hybridization in nine patients (1800 cells) who underwent mastectomy. We selected two tissue samples from each patient, one corresponding to the invasive ductal carcinoma (IDC) and the other adjacent to the intraductal proliferative lesion (IPL). Breast tissue from 17 autopsy samples (1700 cells) was used as a control. The number of cells with monosomy, disomy and polysomy per subject and type of tissue were compared among the three groups of tissue with the RxC statistical software package using 50,000 total replicates. Chromosome 8 aneusomy was found in 66 and 67% of cells from the IDC and IPL samples, respectively. Monosomy was detected significantly more frequently in IPL compared with IDC samples (49.11 vs. 27.11%; p=0.0000), whereas polysomy was significantly more frequent in IDC compared with IPL samples (40.11 vs. 16.99%; p=0.00000). Control cells showed 92.3% disomy. These findings suggest that polysomy of chromosome 8 is more frequently observed in IDC and that monosomy is more frequent in tissue of IPL. Therefore, monosomy may be considered as a primary preneoplastic event. Future studies should be performed to increase the amount of breast tissue with ductal proliferative changes and with cancer, in order to support the results of this pilot study.

DNA damage in women with cervical neoplasia evaluated by DNA breakage detection-fluorescence in situ hybridization.

OBJECTIVE: To evaluate the association between the progressive stages of cervical dysplasia and DNA damage. STUDY DESIGN: A hospital-based, unmatched case-control study was performed. DNA damage levels in the cervical epithelial cells of 30 women (10 with low-grade squamous intraepithelial lesions [LSIL], 10 with high-grade SIL [HSILI, and 10 with no cervical lesions) were evaluated using the DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) technique. DNA damage levels were measured quantitatively using image analysis after whole-genomic DNA hybridization. RESULTS: LSIL patients presented a hybridization signal 20 times greater than the signal in control individuals, which reflected the basal level of DNA damage detected, and HSIL patients showed 100 times the basal control signal. The Kruskal-Wallis test showed differences between both patient groups and the control and between the patients with LSIL and HSIL. CONCLUSION: The DBD-FISH technique is easy to apply to cervical scrapings and provides prompt results. Our findings confirm that the grade of a cervical lesion correlates with the degree of genomic instability.

[Nutritional indicators in children with acute lymphoblastic leukemia]. / Indicadores nutricionales en niños con leucemia linfoblástica aguda.

BACKGROUND: A nutritional assessment allows to determine the state of nutrition and to predict the possibility of displaying additional risks for a disease. Previous investigations have verified that it is not sufficient for children with acute lymphoblastic leukemia (ALL) to have registry of anthropometric measurements such as age, weight, and height. Given the previous information, it is necessary to conduct studies with nutritional indicators that contribute to understanding their importance in children with ALL. OBJECTIVE: To compare the nutritional values of five indicators of children with and without ALL. METHODS: A sample of 21 children with a diagnosis of ALL and 54 children without ALL (control) participated in the study; the children's ages ranged between 1.3 to 10 years. Comparisons between cases and controls were performed. RESULTS: Indicators of albumin and triceps skin fold showed differences between the groups (p < 0.005). CONCLUSIONS: Children with ALL at time of diagnosis had nutritional deficiencies of subcutaneous fat reserve and protein. These indicators could be part of the prognostic and standard of care for children with this cancer.

DNA damage in Mexican women with cervical dysplasia evaluated by comet assay.

OBJECTIVE: To investigate the association between the progressive stage of cervical dysplasia and DNA damage by comet assay. STUDY DESIGN: A hospital-based, unmatched, case-control study was performed. DNA damage levels (none, low, medium and high) in the cervical epithelial cells of 31 women (10 with low grade squamous intraepithelial lesions [LSIL], 10 with high grade [HSIL] and 11 with no cervical lesion) were evaluated using the comet assay. RESULTS: A significant increase in medium DNA damage was observed in women with HSIL (17 +/- 8.9) relative to that in the control women (9 +/- 6.1). A significant increase in high DNA damage was also observed in women with LSIL (23 +/- 15.4) or HSIL (32 +/- 13.1) relative to that in the control women (12 +/- 7.9). CONCLUSION: These findings confirm that the grade of a cervical lesion correlates with the degree of genomic instability.

Epidemiología genética de la obesidad en el noreste de México: Búsqueda de familias nucleares informativas / Epidemiological genetics of obesity in Northeast Mexico: Ascertainment of nuclear informative families

Los objetivos generales de este estudio descriptivo en núcleos familiares fueron: 1) conocer la distribución del estado nutricio de los progenitores con respecto al estado nutricio de sus descendientes y 2) conocer los progenitores que tienen una frecuencia mayor de descendientes con riesgo de sobrepeso (RS) y sobrepeso (S). Se determinó en una muestra de 126 núcleos familiares el índice de masa corporal (IMC) de los progenitores (kappa = 0.95) y descendientes (kappa = 0.97). De todos los progenitores se conocía el lugar de nacimiento de sus cuatro abuelos. Se encontró una amplia variabilidad en el estado nutricio a partir del IMC de los 252 progenitores (Normal-Normal, Normal Obeso, etc.) y sus 300 descendientes (Desnutrido, Normal, RS y S). Se encontró un menor número de descendientes con RS y S (7.7%) en los progenitores con un estado nutricio Normal Normal (grupo de referencia) en comparación con los descendientes de progenitores con Sobrepeso Sobrepeso (22%) y Sobrepeso-Obesidad (35%). El hecho de haber encontrado que los núcleos familiares cuyos progenitores con Sobrepeso Sobrepeso y Sobrepeso Obeso tienen mayor proporción de descendientes con RS y S, nos facilitará en futuros estudios la búsqueda de genes de susceptibilidad para la obesidad en núcleos familiares Mexicanos.

The aims of this descriptive study in nuclear families were: 1) assess the distribution of nutritional stage of parents with respect to the nutritional stage of their children and 2) analyze those parents with the highest frequency of children at risk of being overweight (RS) and overweight (S). Body mass index (BMI) was determined in a sample of 126 nuclear families. Kappa values for parents and children were 0.95 and 0.97, respectively. For parents, birthplace of four grandparents was known. A wide variability in the nutritional stage (assessed by BMI) of the 252 parents (Normal-Normal, Normal Obese, etc.) and their 300 children (Undernourished, Normal, RS and S) was found. A minimum number of children with RS and S (7.7%) was found among parents with Normal Normal nutritional stage (reference group) in comparison with children whose parents were Overweight-Overweight (22%) and Overweight Obese (35%). Since we found in parents Overweight-Overweight and Overweight Obese a greater proportion of children with RS and S, this finding will facilitate the search for susceptibility genes for obesity in Mexican nuclear families with these characteristics.

Association between the stages of cervical cancer and chromosome 1 aneusomy.

The high-risk human papillomavirus is known to play a pivotal role in cervical carcinogenesis. Numerical and structural aberrations are known to be related to different behaviors of malignant cervical lesions. The aims of this study were (1) to assess the number of cervical cells with chromosome 1 aneusomy (monosomy, trisomy, and tetrasomy) in 20 women with cervical intraepithelial neoplasia (CIN 1, CIN 2, CIN 3, and invasive cancer) and three women without CIN by fluorescence in situ hybridization (FISH), (2) to determine the heterogeneity of aneusomy among women within each of the five groups studied, (3) to determine the association between the four progressive stages of cervical cancer and the number of cells with and without aneusomy, (4) to determine the association between number of cells with and without aneusomy and human papilloma virus (HPV) infection, and (5) to determine its usefulness as a biomarker of cancer risk. A hospital-based unmatched case-control study in a sample of 23 women grouped by disease stage and selected by histology from the Obstetrics and Gynecology Hospital of the Instituto Mexicano del Seguro Social (IMSS) in Mexico was conducted in 2002. Numerical aberrations of chromosome 1 in cervical smears were detected with FISH. HPV was detected with polymerase chain reaction (PCR) and typing was performed with restriction fragment length polymorphism (RFLPs). Analysis of chromosome 1 aneusomy revealed (1) homogeneity among women within each one of the five groups, (2) a positive linear trend between the aneusomy frequency and grade of lesion, and (3) an association between aneusomy and high-risk HPV infection. These findings suggest the usefulness of the number of cervical cells with chromosome 1 aneusomy as a biomarker. In order to validate this biomarker we suggest a larger prospective study of cytological samples of patients with a longer follow-up.

Alteraciones cromosómicas secundarias en pacientes con leucemia mieloide crónica, en un hospital de referencia del noreste de México / Secondary Chromosomic Changes in Patients with Myeloid Leukemia in a Reference Hospital in Northeastern Mexico

Introducción: la caracterización del perfil citogenético que presenta una determinada fase de la leucemia mieloide crónica (LMC), está ofreciendo nuevas direcciones para la investigación de la etiología a nivel molecular. En México no existen datos de la descripción cromosómica de esta enfermedad, por lo que el objetivo del presente estudio fue determinar las alteraciones cromosómicas de 56 pacientes con LMC. Diseño: estudio transversal (diagnóstico y estadio). Material y métodos: las muestras de médula ósea de 56 pacientes con LMC en diferentes etapas, fueron sometidas a estudios citogenéticos mediante técnicas de bandeo G e hibridación in situ fluorescente (FISH), con sonda específica para cromosoma Filadelfia (Ph). Resultados: 19% (6/31) de los pacientes en etapa crónica mostró alteraciones cromosómicas secundarias, en contraste con 60% (15/25) observado en aquellos pacientes en etapa acelerada. Las alteraciones cromosómicas secundarias más frecuentes fueron: las trisomías 8 y 19, cromosoma Ph extra e isocromosoma de brazos largos del cromosoma 17. Conclusión: este es el primer trabajo que determina alteraciones cromosómicas secundarias en pacientes mestizos mexicanos con LMC, cuyas frecuencias están de acuerdo con lo reportado para otras poblaciones a nivel mundial.

Introduction: Our aim was to characterize the cytogenetic profile that displays a certain phase of chronic myelogenous leukemia (CML), offering new directions for investigation of the etiology to the molecular level. In Mexico, data does not exist in this regard; thus, the objective of the present study was to determine cytogenetic alterations in 56 Mestizo Mexican patients with LMC. Design: Cross-sectional study (diagnosis and stage) was carried out. Materials and Methods: samples of bone marrow of 56 patients with CML in different phases were analyzed using G banding and fluorescence in situ hybridization (FISH) with DNA probes for Philadelphia chromosome (Ph). Results: 19% of patients in chronic stage showed secondary chromosomal alterations in contrast with an observed 60% in patients in accelerated stage. Most frequent alterations included trisomy 8 and 19, extra Ph chromosome, and isochromosome of thell. Conclusions: We believe this to be the first work that determines secondary chromosomal alterations in Mexican racially mixed patients with LMC. These are in agreement with those reported for other populations at the worldwide level.