PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Comparative Genomics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

Genomic alterations in renal tumours: what have we learned in the era of comparative genomic hybridisation?

One of the major challenges in cancer research is to generate molecular profiles of tumours and establish correlations between genetic changes and clinical parameters by screening technologies. The identification of tumour-specific gene targets has potential diagnostic and therapeutic implications. Metaphase comparative genomic hybridisation has been used to detect relative DNA-sequence copy number gains (including high-level amplifications of chromosomal regions) and copy number losses in human neoplasms. In the past, metaphase comparative genomic hybridisation has been shown to be a powerful genome-wide screening method and this has considerably advanced our understanding of renal cancer biology. Novel molecular technologies, including array-based comparative genomic hybridisation, fluorescence in situ hybridisation (FISH), cDNA and tissue microarrays will serve to facilitate further characterisation of candidate genes residing in chromosomal regions defined by metaphase comparative genomic hybridisation. This review concentrates on the application of metaphase comparative genomic hybridisation in the area of renal cancer research and summarises data obtained from comparative genomic hybridisation studies.

Gene Dosage↗

An isothermal method for whole genome amplification of fresh and degraded DNA for comparative genomic hybridization, genotyping and mutation detection.

Molecular genotyping has important biomedical and forensic applications. However, limiting amounts of human biological material often yield genomic DNA (gDNA) in insufficient quantity and of poor quality for a reliable analysis. This motivated the development of an efficient whole genome amplification method with quantitatively unbiased representation usable on fresh and degraded gDNA. Amplification of fresh frozen, formalin-fixed paraffin-embedded (FFPE) and DNase-degraded DNA using degenerate oligonucleotide-primed PCR or primer extension amplification using a short primer sequence bioinformatically optimized for coverage of the human genome was compared with amplification using current primers by chromosome-based and BAC-array comparative genomic hybridization (CGH), genotyping at short tandem repeats (STRs) and single base mutation detection. Compared with current primers, genome amplification using the bioinformatically optimized primer was significantly less biased on CGH in self-self hybridizations, and replicated tumour genome copy number aberrations, even from FFPE tissue. STR genotyping could be performed on degraded gDNA amplified using our technique but failed with multiple displacement amplification. Of the 18 different single base mutations 16 (89.5%) were correctly identified by sequencing gDNA amplified from clinical samples using our technique. This simple and efficient isothermal method should be helpful for genetic research and clinical and forensic applications.

Base Sequence↗

Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia.

Non-isolated congenital diaphragmatic hernia (CDH+) is a severe birth defect that is often caused by de novo chromosomal anomalies. In this report, we use genome-wide oligonucleotide-based array comparative genome hybridization (aCGH) followed by rapid real-time quantitative PCR analysis to identify, confirm and map chromosomal anomalies in a cohort of 26 CDH+ patients. One hundred and five putative copy number changes were identified by aCGH in our cohort of CDH+ patients. Sixty-one of these changes (58%) had been previously described in normal controls. Twenty of the remaining 44 changes (45%) were confirmed by quantitative real-time PCR or standard cytogenetic techniques. These changes included de novo chromosomal abnormalities in five of the 26 patients (19%), two of whom had previously normal G-banded chromosome analyses. Data from these patients provide evidence for the existence of CDH-related genes on chromosomes 2q37, 6p22-25 and 14q, and refine the CDH minimal deleted region on 15q26 to an interval that contains COUP-TFII and only eight other known genes. Although COUP-TFII is likely to play a role in the development of CDH in patients with 15q26 deletions, we did not find COUP-TFII mutations in 73 CDH samples. We conclude that the combination of oligonucleotide-based aCGH and quantitative real-time PCR is an effective method of identifying, confirming and mapping clinically relevant copy number changes in patients with CDH+. This method is more sensitive than G-banded chromosome analysis and may find wide application in screening patients with congenital anomalies.

Chromosome Aberrations↗

Screening of genomic imbalances in glioblastoma multiforme using high-resolution comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that allows the genome-wide analysis of DNA sequence copy number differences. We applied conventional CGH and the recently developed high-resolution CGH (HR-CGH) to tumour samples from 18 patients with glioblastoma multiforme (GBM) in order to compare the sensitivity of CGH and HR-CGH in the screening of chromosomal abnormalities. The abnormalities were studied in topologically different central and peripheral tumour parts. A total of 78 different changes were observed using CGH (0-16 per tumour, median 3.5) and 154 using HR-CGH (0-21 per tumour, median 6). Using HR-CGH, losses were more frequent than gains. The representation of the most prominent changes revealed by both methods was similar and was comprised of the amplification of 7q12 and 12q13-q15, the gain of 7, 3q and 19, and the loss of 10, 9p, and 13q. However, HR-CGH detected certain other abnormalities (the loss of 6, 14q, 15q and 18q, and the gain of 19), which were rarely revealed by CGH. Using HR-CGH, the numbers and types of chromosomal changes detected in the central and peripheral parts of GBM were almost the same. The loss of chromosomes 10 and 9p and the gain of chromosomes 7 and 19 were the most frequent chromosomal alterations in both tumour parts. Our results from the GBM analysis show that HR-CGH technology can reveal new, recurrent genetic alterations involving the genes known to participate in tumorigenesis and in the progression of several human malignancies, thus allowing for a more accurate genetic characterization of these tumours.

Adult↗

Combining comparative genomics with de novo motif discovery to identify human transcription factor DNA-binding motifs.

BACKGROUND: As more and more genomes are sequenced, comparative genomics approaches provide a methodology for identifying conserved regulatory elements that may be involved in gene regulations. RESULTS: We developed a novel method to combine comparative genomics with de novo motif discovery to identify human transcription factor binding motifs that are overrepresented and conserved in the upstream regions of a set of co-regulated genes. The method is validated by analyzing a well-characterized muscle specific gene set, and the results showed that our approach performed better than the existing programs in terms of sensitivity and prediction rate. CONCLUSION: The newly developed method can be used to extract regulatory signals in co-regulated genes, which can be derived from the microarray clustering analysis.

Amino Acid Motifs↗

Extensive genomic abnormalities in childhood medulloblastoma by comparative genomic hybridization.

We analyzed 27 samples of primary medulloblastoma, using comparative genomic hybridization and a novel statistical approach to evaluate chromosomal regions for significant gain or loss of genomic DNA. An array of nonrandom changes was found in most samples. Two discrete regions of high-level DNA amplification of chromosome bands 5p15.3 and 11q22.3 were observed in 3 of 27 tumors. Nonrandom genomic losses were most frequent in regions on chromosomes 10q (41% of samples), 11 (41%), 16q (37%), 17p (37%), and 8p (33%). Regions of DNA gain most often involved chromosomes 17q (48%) and 7 (44%). These findings suggest a greater degree of genomic imbalance in medulloblastoma than has been recognized previously and highlight chromosomal loci likely to contain oncogenes or tumor suppressor genes that may contribute to the molecular pathogenesis of this tumor.

Adolescent↗

Automated screening for genomic imbalances using matrix-based comparative genomic hybridization.

Genome-wide screening for chromosomal imbalances using comparative genomic hybridization (CGH) revealed a wealth of data on previously unrecognized tumor-specific genomic alterations. CGH to microarrays of DNA, an approach termed matrix-CGH, allows detection of genomic imbalances at a much higher resolution. We show that matrix CGH is also feasible from small tissue samples requiring universal amplification of genomic DNA. Because widespread application of matrix-CGH experiments using large numbers of DNA targets demands a high degree of automation, we have developed a protocol for a fully automated procedure. The use of specialized instrumentation for the generation of DNA chips, their hybridization, scanning, and evaluation required numerous alterations and modifications of the initial protocol. We here present the elaboration and testing of automated matrix-CGH. A chip consisting of 188 different genomic DNA fragments, cloned in bacterial artificial chromosome (BAC) or P1-derived artificial chromosome (PAC) vectors and immobilized in replicas of 10, was used to assess the performance of the automated protocol in determining the gene dosage variations in tumor cell lines COLO320-HSR, HL60, and NGP. Although ratios of matrix-CGH were highly concordant with results of chromosomal CGH (85%), the dynamic range of the matrix-CGH ratios was highly superior. Investigation of the two amplicons on 8q24 in COLO320-HSR and HL60, containing the MYC gene, revealed a homogeneous amplicon in COLO320-HSR but a heterogeneous amplification pattern in HL60 cells. Although control clones for normalization of the signal ratios can be predicted in cases with defined chromosomal aberrations, in primary tumors such data are often not available, requiring alternative normalization algorithms. Testing such algorithms in a primary high-grade B-cell lymphoma, we show the feasibility of this approach. With the matrix-CGH protocol presented here, robust and reliable detection of genomic gains and losses is accomplished in an automated fashion, which provides the basis for widespread application in tumor and clinical genetics.

Chromosome Aberrations↗

Atypical endometrial hyperplasia shares genomic abnormalities with endometrioid carcinoma by comparative genomic hybridization.

Endometrial hyperplasia is a common disorder that is now observed with increasing frequency in women treated with hormonal replacement therapy or with tamoxifen. This study was undertaken to determine whether genomic features of various forms of endometrial hyperplasias would allow their classification as a benign, premalignant, or malignant abnormality. Comparative genomic hybridization (CGH) was performed on endometrial glands microdissected by laser capture microscope from 19 archival endometrial samples, comprising 5 normal endometria, 1 polyp, 2 simple hyperplasias, 5 hyperplasias with nuclear abnormalities (atypical hyperplasias), and 4 low-grade and 2 high-grade endometrioid carcinomas, 1 with squamous component (adenoacanthoma). Genomic DNA, extracted from the glands and the squamous component in 1 case, was amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and compared with sex-matched DNA by CGH. No genomic imbalances were observed in the normal samples, the polyp, or the simple hyperplasias. However, in atypical hyperplasia, regardless of the level of cytologic atypia, genomic abnormalities were observed that also occurred in endometrioid carcinomas. Chromosomes 1, 8, and 10 were most often affected. The results are compared with molecular genetic abnormalities recently reported in these lesions. This study strongly suggests that atypical endometrial hyperplasias are closely related to endometrioid carcinoma and should be considered precancerous lesions, contrary to simple hyperplasia, which is a benign disorder. The squamous component of one of the high-grade carcinomas showed genetic abnormalities similar to those of endometrioid carcinoma and therefore does not represent squamous metaplasia but is an integral part of the malignant process.

Adult↗

Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization.

BACKGROUND/AIMS: Our recent analysis of gastric cancers and colorectal cancers using comparative genomic hybridization revealed a novel, high frequent copy number increases the long arm of chromosome 20 in association with possible involvement of liver metastases and poor prognosis. This led to further comparative genomic hybridization analysis of chromosomal aberrations in primary tumors of esophageal squamous cell carcinoma. The aim of the study presented here was to analyze the chromosomal aberrations and to determine the numbers of copies of AIB1, BTAK, DcR3 and E2F1 as putative target genes on chromosome 20q as well as their expression and relation to clinicopathological features in 41 primary tumors of esophageal squamous cell carcinoma. METHODOLOGY: We used comparative genomic hybridization to screen 41 primary tumors of esophageal squamous cell carcinoma for changes in the number of copies of DNA sequences. To further characterize the gain of DNA sequences at 20q, we also performed fluorescence in situ hybridization analysis. We examined the relationship between these changes and clinicopathological factors. RESULTS: Gains in chromosome arm 20q were detected (34.1%) as well as a high level of gain in 20q12-13 (4.8%). AIB1 amplification was observed in 4.9% (2/41), BTAK amplification in 9.8% (4/41), DcR3 amplification was in 4.9% (2/41), and E2F1 amplification in 7.3% (3/41). The survival of patients with BTAK or E2F1 amplification was significantly lower than that of patients without these abnormalities. CONCLUSIONS: These findings provide evidence for a number of previously unknown genomic aberrations in esophageal squamous cell carcinoma, suggesting the existence of target regions relevant to its progression. Esophageal squamous cell carcinoma with 20q gain showed extensive lung metastases, pleural effusion and liver metastases and poorer prognosis compared to cases without 20q gain. Our results suggest that amplification of BTAK or E2F1 are likely to lead to an increase in the number of malignant phenotypes of esophageal squamous cell carcinoma and that these aberrations can be expected to be useful as markers of poor prognosis.

Aged↗

Evaluation of Phi29-based whole-genome amplification for microarray-based comparative genomic hybridisation.

For the optimal performance of high throughput genomic technologies sufficient yields of high-quality DNA are crucial. Following microdissection, most samples fail to produce sufficient quantities of DNA for genome-wide experiments. Various PCR-based amplification methods have been used, but these usually produce nonuniform representations of the genome. Bacteriophage Phi29 DNA polymerase random-primed DNA amplification is based on isothermal multiple displacement amplification. We sought to define the genome representation of this method in a bacterial artificial chromosome microarray comparative genomic hybridisation (aCGH) platform. Test genomic female DNA was amplified using Phi29 amplification at four different starting concentrations (0.5, 5, 10 and 50 ng). These products were combined with unamplified and amplified genomic female DNA as reference. In addition, 50 ng of DNA from five microdissected breast cancer frozen samples, were amplified using the same method. Three combinations were performed: unamplified test with unamplified reference, amplified test with unamplified reference and both amplified tumour and reference DNA. aCGH was performed with an in-house 16 K BAC platform (a resolution of approximately 100 Kb). Pearson's correlation tests and hierarchical clustering were performed to compare the profiles obtained. aCGH profiles obtained with amplified test and unamplified reference female genomic DNA showed copy number biases throughout the genome. These biases were more conspicuous with smaller amounts of starting material and mapped to regions of known copy number polymorphisms. When similar concentrations of test and reference DNA were amplified, the biases were significantly reduced, rendering accurate profiles. For the tumours, representative profiles were obtained when both test and reference DNA were amplified. Phi29 amplification induces copy number biases and unamplified material remains the gold standard for copy number analysis. For accurate results using Phi29 amplification, samples subjected to aCGH analysis should be combined with reference DNA amplified with the same method, using similar amounts of starting template.

Breast Neoplasms↗

Genolevures complete genomes provide data and tools for comparative genomics of hemiascomycetous yeasts.

The Génolevures online database (http://cbi.labri.fr/Genolevures/) provides tools and data relative to 4 complete and 10 partial genome sequences determined and manually annotated by the Génolevures Consortium, to facilitate comparative genomic studies of hemiascomycetous yeasts. With their relatively small and compact genomes, yeasts offer a unique opportunity for exploring eukaryotic genome evolution. The new version of the Génolevures database provides truly complete (subtelomere to subtelomere) chromosome sequences, 25 000 protein-coding and tRNA genes, and in silico analyses for each gene element. A new feature of the database is a novel collection of conserved multi-species protein families and their mapping to metabolic pathways, coupled with an advanced search feature. Data are presented with a focus on relations between genes and genomes: conservation of genes and gene families, speciation, chromosomal reorganization and synteny. The Génolevures site includes an area for specific studies by members of its international community.

Databases, Genetic↗

Gains on 9p are common genomic aberrations in idiopathic myelofibrosis: a comparative genomic hybridization study.

Ideopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder resulting in bone marrow fibrosis as a consequence of growth factor release from clonal haematopoiesis. Conventional cytogenetic analysis identifies abnormalities in approximately a third of cases at diagnosis, although rarely uncovers unique, primary genetic events. We have used comparative genomic hybridization (CGH) to study 25 IMF cases and have compared the results with conventional cytogenetics. Metaphase cells were available for analysis in 13 cases, of which seven showed an abnormal karyotype. CGH chromosomal profiles showed imbalances in 21 of 25 cases. The most frequent aberrations were gains of 9p (12 cases), 2q (seven cases), 3p (seven cases), chromosome 4 (seven cases), 12q (seven cases), 13q (eight cases). The main losses were at 17q and occurred in six cases. The results for CGH and cytogenetics were matched for one case only. Investigation of IMF by CGH suggests that genomic aberrations are much more common than has been previously indicated by conventional cytogenetic analysis and occur in the majority of cases. Gains of 9p were the most frequent finding, occurring in 50% of patients and suggests that genes on 9p may play a crucial role in the pathogenesis of IMF.

Aged↗

Gains, losses, and amplification of genomic material in rhabdomyosarcoma analyzed by comparative genomic hybridization.

In this study, 10 embryonal and 14 alveolar rhabdomyosarcoma (RMS) tumor samples, including 4 cell lines derived from tumors of the alveolar subtype, were analyzed by comparative genomic hybridization. In the embryonal tumors, the gain of whole or most of various chromosomes, notably chromosomes 2 (60% of cases), 13 (60%), 12 (60%), 8 (60%), 7 (50%), 17 (40%), 18 (40%), and 19 (40%), and the loss of chromosomes 16 (40%), 10 (30%), 15 (20%), and 14 (20%) were found. One case showed evidence of genomic amplification at 12q13-15. In contrast, the alveolar tumors and cell lines showed consistent evidence of genomic amplification, with multiple amplicons in some cases. The amplicons were localized to l2q13-15 (50%), 2p24 (36%), 13q14 (14%), l3q32 (14%), 1q36 (14%), 1q21 (7%), and 8q13-21 (7%). Four cases had additional copies of chromosome 17 or l7q. These changes were in addition to the presence of fusion gene transcripts that are associated with translocations specific to alveolar RMS. The results show that distinct patterns of primarily gains of specific chromosomal material are associated with the embryonal subtype of RMS, and that genomic amplification seems to play an important role in the alveolar subtype. Notably, these distinct changes predominantly involved chromosomes 2, 12, and 13 in both subtypes.

Adolescent↗

High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines.

Tumours develop from clonally expanded population of cells harbouring aberrations of oncogenes and tumour suppressor genes. In this study, metaphase and array comparative genomic hybridization showed good correlation of aberration profiles in lung adenocarcinoma cell lines from patients with different tobacco exposure. Recurrent DNA gains were found at chromosomes 1, 7, 8, 17, 20, and deletions at 1, 3, 8, 9, 10, 12, 17, 18, 19. Candidate tumour loci and encompassed genes at 7p21 (AGR2), 8q21(TPD52), 20q13 (ZNF217, WFDC2, EEF1A2) and 10p15 (KLF6) were analyzed by dual colour FISH for genomic changes and quantitative PCR for expression changes. Results indicated that EEF1A2 and KLF6 were strong candidates of oncogene and tumour suppressor genes, respectively. This study illustrates, a practical strategy for identifying candidate cancer genes from microarray data.

Adenocarcinoma↗

A genome sequence survey of the filarial nematode Brugia malayi: repeats, gene discovery, and comparative genomics.

Comparative nematode genomics has thus far been largely constrained to the genus Caenorhabditis, but a huge diversity of other nematode species, and genomes, exist. The Brugia malayi genome is approximately 100 Mb in size, and distributed across five chromosome pairs. Previous genomic investigations have included definition of major repeat classes and sequencing of selected genes. We have generated over 18,000 sequences from the ends of large-insert clones from bacterial artificial chromosome libraries. These end sequences, totalling over 10 Mb of sequence, contain just under 8 Mb of unique sequence. We identified the known Mbo I and Hha I repeat families in the sequence data, and also identified several new repeats based on their abundance. Genomic copies of 17% of B. malayi genes defined by expressed sequence tags have been identified. Nearly one quarter of end sequences can encode peptides with significant similarity to protein sequences in the public databases, and we estimate that we have identified more than 2700 new B. malayi genes. Importantly, 459 end sequences had homologues in other organisms, but lacked a match in the completely sequenced genomes of Caenorhabditis briggsae and Caenorhabditis elegans, emphasising the role of gene loss in genome evolution. B. malayi is estimated to have over 18,500 protein-coding genes.

Animals↗

Alfresco--a workbench for comparative genomic sequence analysis.

Comparative analysis of genomic sequences provides a powerful tool for identifying regions of potential biologic function; by comparing corresponding regions of genomes from suitable species, protein coding or regulatory regions can be identified by their homology. This requires the use of several specific types of computational analysis tools. Many programs exist for these types of analysis; not many exist for overall view/control of the results, which is necessary for large-scale genomic sequence analysis. Using Java, we have developed a new visualization tool that allows effective comparative genome sequence analysis. The program handles a pair of sequences from putatively homologous regions in different species. Results from various different existing external analysis programs, such as database searching, gene prediction, repeat masking, and alignment programs, are visualized and used to find corresponding functional sequence domains in the two sequences. The user interacts with the program through a graphic display of the genome regions, in which an independently scrollable and zoomable symbolic representation of the sequences is shown. As an example, the analysis of two unannotated orthologous genomic sequences from human and mouse containing parts of the UTY locus is presented.

Algorithms↗

Comparative genomic analysis of a novel heat-tolerant and euryhaline strain of unicellular marine cyanobacterium Cyanobacterium sp. DS4 from a high-temperature lagoon.

BACKGROUND: Cyanobacteria have diversified through their long evolutionary history and occupy a wide range of environments on Earth. To advance our understanding of their adaptation mechanisms in extreme environments, we performed stress tolerance characterizations, whole genome sequencing, and comparative genomic analyses of a novel heat-tolerant and euryhaline strain of the unicellular cyanobacterium Cyanobacterium sp. Dongsha4 (DS4). This strain was isolated from a lagoon on Dongsha Island in the South China Sea, a habitat with fluctuations in temperature, salinity, light intensity, and nutrient supply. RESULTS: DS4 cells can tolerate long-term high-temperature up to 50 ℃ and salinity from 0 to 6.6%, which is similar to the results previously obtained for Cyanobacterium aponinum. In contrast, most mesophilic cyanobacteria cannot survive under these extreme conditions. Based on the 16S rRNA gene phylogeny, DS4 is most closely related to Cyanobacterium sp. NBRC102756 isolated from Iwojima Island, Japan, and Cyanobacterium sp. MCCB114 isolated from Vypeen Island, India. For comparison with strains that have genomic information available, DS4 is most similar to Cyanobacterium aponinum strain PCC10605 (PCC10605), sharing 81.7% of the genomic segments and 92.9% average nucleotide identity (ANI). Gene content comparisons identified multiple distinct features of DS4. Unlike related strains, DS4 possesses the genes necessary for nitrogen fixation. Other notable genes include those involved in photosynthesis, central metabolisms, cyanobacterial starch metabolisms, stress tolerances, and biosynthesis of novel secondary metabolites. CONCLUSIONS: These findings promote our understanding of the physiology, ecology, evolution, and stress tolerance mechanisms of cyanobacteria. The information is valuable for future functional studies and biotechnology applications of heat-tolerant and euryhaline marine cyanobacteria.

Cyanobacteria↗

A preliminary investigation of genomic screening in cervical carcinoma by comparative genomic hybridization.

BACKGROUND & OBJECTIVE: Available clinical, radiological and histopathologic risk factors are not adequate for accurate prognosis in uterine cervix carcinoma. Hence there is a need to identify indicators to select high risk cases. Most cancers occur and progress through step-wise somatic genetic mutations. Thus screening of whole genome for specific genomic alterations and its outcome following treatment may predict prognosis. The present study was carried out to investigate genomic alterations associated with cervical carcinoma and any association of genomic alterations with clinico-pathologic parameters. METHODS: Cervical carcinoma cases (n = 4) were subjected to protocol based clinical evaluation, treatment and follow up as a double blind procedure. Tumour samples were collected before radiotherapy and 3 months after completion of radiotherapy. All the samples were stored at -80 degrees C. Comparative genomic hybridization (CGH) was carried out to screen genomic alterations in all tumour samples obtained before treatment. Conventional fluorescent in situ hybridization (FISH) was carried out to confirm the CGH findings and to follow up post-treatment samples. Patients were followed up for a minimum of one year or until death. RESULTS: The CGH analysis identified genomic losses and gains. The gains were observed mainly in chromosomes 1q 25.1, 3q 26.1, 6q 13-16, 9p 22 and X, and losses in chromosome 10 and 11q21-24. CGH and FISH results were complementary to each other. Of the four patients, two were alive and two were dead at the end of follow up. INTERPRETATION & CONCLUSION: Initial results indicated that persistence of genomic alterations and appearance of giant nucleus was associated with poor prognosis and the same may be used to follow up patient. Similar studies on large sample with longer period of follow up are warranted to validate our result.

Carcinoma↗