Mohammed Kamal

A Genome-Wide Study of Cytogenetic Changes in Colorectal Cancer Using SNP Microarrays: Opportunities for Future Personalized Treatment

In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor and surrounding healthy) fresh frozen tissue from 86 CRC patients using Illuminas Infinium-based SNP array. This method allowed us to study CIN in CRC, with simultaneous analysis of copy number (CN) and B-allele frequency (BAF) - a representation of allelic composition. These data helped us to detect mono-allelic and bi-allelic amplifications/deletion, copy neutral loss of heterozygosity, and levels of mosaicism for mixed cell populations, some of which can not be assessed with other methods that do not measure BAF. We identified associations between CN abnormalities and different CRC phenotypes (histological diagnosis, location, tumor grade, stage, MSI and presence of lymph node metastasis). We showed commonalities between regions of CN change observed in CRC and the regions reported in previous studies of other solid cancers (e.g. amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From Therapeutic Target Database, we identified relevant drugs, targeted to the genes located in these regions with CN changes, approved or in trials for other cancers and common diseases. These drugs may be considered for future therapeutic trials in CRC, based on personalized cytogenetic diagnosis. We also found many regions, harboring genes, which are not currently targeted by any relevant drugs that may be considered for future drug discovery studies. Our study shows the application of high density SNP arrays for cytogenetic study in CRC and its potential utility for personalized treatment.

Genital human papillomavirus infection among women in Bangladesh: findings from a population-based survey.

Background There has been no population-based study on human papillomavirus (HPV) prevalence or its genotypes in Bangladesh; a country eligible for GAVI funding for HPV vaccine. Methods We used baseline survey data of a prospective cohort study that was conducted in one urban and one rural area of Bangladesh. A total of 997 urban and 905 rural married women, aged 13 to 64 years, were enrolled in the baseline during July-December, 2011. Information was collected on socio-demographic characteristics and potential risk factors for HPV infection followed by gynecological examination and collection of endocervical samples using the cervical cytobrush (Digene cervical sampler). HPV DNA testing was done by Polymerase Chain Reaction (PCR) using a consensus primer set. Results Prevalence of any HPV infection was 7.7% with no significant difference between urban and rural women. Most common high-risk genotypes were HPV16, HPV66, HPV18, HPV45, HPV31 and HPV53. Urban women working as housemaids or garment workers were at higher risk of any HPV infection (OR = 2.15, 95% CI: 1.13–4.11) compared to housewives. Rural women whose husband lived overseas were almost two times more likely to have any HPV infection (OR = 1.93; 95% CI 1.05–3.55) compared to women whose husbands lived with them. Conclusion The prevalence of HPV infection among Bangladeshi women is similar to other regions of Asia. However, type-specific patterns are different. The study findings will inform the formulation of HPV vaccination policies in Bangladesh, monitoring the impact of vaccination programmes, and the identification of target populations for screening.

Drug induced hepatic focal nodular hyperplasia.

Focal nodular hyperplasia, an uncommon benign hepatic tumor, has been reported following ingestion of various drugs and chemical agents. The authors report a case of a young girl who developed such lesion following ingestion of antituberculosis drugs for the treatment of her abdominal tuberculosis.

Perforation of jejunal duplication lined with ectopic gastric mucosa

Abstract:  Alimentary tract duplications are rare congenital anomalies that occasionally contain ectopic gastric mucosa that secretes acid peptic juice and can cause pain, ulceration, bleeding and rarely perforation. We report a case of a 2‐year‐old girl who developed perforation of a jejunal duplication lined with ectopic gastric mucosa who was managed surgically.

Isolated Intracranial Rosai-Dorfman Disease.

Background. Rosai-Dorfman disease (RDD) is a benign histiocytic proliferative disorder of unknown etiology. This rare condition commonly causes massive cervical lymphadenopathy. Intracranial RDD without any nodal involvement is extremely rare. Case Report. A young Bangladeshi male complained of bilateral complete blindness with left sided deafness for about three years. There was no lymphadenopathy. MRI and CT scan of brain suggested an inflammatory/neoplastic (?meningioma) lesion located at left parasellar region which extended frontally to encircle both optic nerves and also to left prepontine area. Histopathologically the lesion was diagnosed as RDD. The patient was treated with steroid and significant clinical improvement observed. Conclusion. The prognosis of intracranial RDD is not poor. It can be treated with surgery with or without corticosteroids, chemotherapy, and so forth. But as the condition is extremely rare and often misdiagnosed, the clinician, radiologist, and histopathologist should have a suspicion in their mind about the possibility of RDD.

The colon and terminal ileum in patients with ankylosing spondylitis and controls in Bangladesh: a macroscopic and microscopic study

Abstract Objective Little is known about gut lesions in AS patients in a developing country, such as Bangladesh. Methods Full colonoscopy, including the terminal ileum, was performed in 60 AS patients and 20 controls, without diarrhoea, to study macroscopic and microscopic lesions. Results In the colon, in 60 AS patients 17 macroscopic lesions were found, of which 11 were in the rectum; only one lesion was found in 20 controls. The prevalence of microscopic lesions in the ascending colon, sigmoid colon and rectum was 51, 44 and 50 in patients, respectively, and 13, 9 and 8 in controls. In the terminal ileum, macroscopic and microscopic lesions were seen in 21/56 and 43/56 AS patients, respectively, and in 1/20 and 9/20 controls. In the AS group, macroscopic (38.5 vs 5%, P < 0.01) and microscopic (76.8 vs 45%, P = 0.009) lesions were more frequent than in controls; no IBD was diagnosed. Findings were comparable in the axial AS group (n = 25) and the mainly peripheral group (n = 35). In AS patients, marked eosinophilic infiltration was observed in the ascending colon and sigmoid colon but not in the rectum, and this infiltration was more than in controls. The colonic mucosa in controls was otherwise comparable with western studies. Anaemia was seen in 18/60 cases. No association was found between anaemia or HLA-B27 status and gut lesions. Conclusion There was an equal percentage of microscopic lesions in the whole gut in AS cases and healthy controls. Previous helminth invasions might have played a role. Lesions differ significantly between AS and controls only in the ileum; therefore, the ileal lesions might be more disease related than the colonic ones.

Hepatoblastoma in a child with dextrocardia and possible histopathological alteration reminiscent of hepatocellular carcinoma after neoadjuvant chemotherapy

It is quite unambiguous and interesting that postchemotherapy histology of hepatoblastoma may mimicry that of hepatocellular carcinoma which should be differentiated by proper immunohistochemistry and cytology, if possible, for further management and predict prognosis.

Inflammatory Myofibroblastic Tumour, an Unusual Presentation in Maxilla and Paranasal Sinuses: Review of Literature and a Case Report

Inflammatory myofibroblastic tumour (IMT) is a rare pathology of unknown etiology. It was called inflammatory pseudotumor (IPT) until 1998, when the term inflammatory myofibroblastic tumour (IMT) was proposed as being a more descriptive name [1]. IMT and IPT terminologies are most confusing and interchangeably used due to very numerous similarities in histological presentations. But despite numerous similarities in histology / subtle differences such as marked spindle cell proliferation in IMT and prominent lymphoplasmacytic infiltration in IPT help to histologically differentiate them. Immunohistochemical markers are invaluable in differentiating both of them. Though there is no significant difference in the clinical standpoint and are considered synonymous [2,3]. Now it is belong to the group of soft tissue tumours and have been known by various synonyms; inflammatory pseudotumor, plasma cell granuloma, fibrous histiocytoma and sometimes low grade sarcoma or inflammatory fibrosarcoma [4-15]. It was referred to by several different terms until the World Health Organization (WHO) classified IMT as a distinct entity [6]. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding its true biologic nature of these lesions [7]. Therefore IMT is clinico-pathologically distinctive but biologically controversial entity, which was originally described as true neoplastic lesion [5-8]. Exact etio-pathogenesis is not known, though it is considered to be an exaggerated inflammatory reaction to tissue injury of unknown cause [9]. Recently the -concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and further cytogenetic evidence of acquired clonal chromosomal abnormalities [10]. Moreover the presence of human herpes virus-8 DNA sequences and the over expression of interleukin 6 and cyclin D1 have been reported in IMTs [11]. Then conception of inflammatory origin was refuted by some researchers. Later it was described may arise as an immunologic host reaction to stimuli such as microorganisms (e.g Epstein –Barr Virus, Human Herpes Virus-8), foreign bodies or neoplastic tissues, chronic inflammation and may even trauma [12]. Though in some studies found an association between trauma and IMT that may lead to reactive inflammation has been suggested but causation cannot be proven completely [10-12]. Therefore whatever the cause a localized derangement in the immune response after the initial insult may be an underlying mechanism [13]. IMT is characterized by solitary, well demarcated mass with fibroblastic or myofibroblastic spindle cell proliferation with varying degrees of inflammatory cell infiltration [1-14]. There are three basic histologic patterns are recognized:

Interaction of KRAS somatic mutation and colorectal carcinoma and its association with differential DNA methylation.

577 Background: We examined if KRAS somatic mutation in colorectal carcinoma (CRC) is associated with differential tumor DNA methylation. Methods: We did a genome-wide methylation assay (450K) for a total of 250 paired samples from 125 CRC patients (m = 72, f = 53) at different stages (stage 1: 25, stage II: 33 and stage III: 67). Of them 101 had left-sided CRC (descending colon to rectum); 30 had MSI, and 34 had somatic mutation in KRAS (rs112445441). Results: Frequency of KRAS mutation was not different between right and left-sided CRC (29% vs. 27%). But, like other series, MSI was more frequent in the right-sided tumor (54% vs. 17%, p = 0.003). In patients with wild type KRAS tumor (n = 91), paired comparison between tumor and corresponding normal tissue identified a total of 1244 tumor-specific differential methylation loci (DML) covering 532 genes that were significant at FDR 0.001 and magnitude of difference ≥ 20%; But similar analysis in patients with KRAS mutation (n = 34) revealed 7612 tumor-spec...

Abstract 2778: Interaction of Microsatellite Instability (MSI) and tumor for Differential DNA Methylation in Colorectal carcinoma

Introduction: Colorectal Cancer (CRC) is one of the most common malignancies worldwide. The role of MSI and KRAS somatic mutation in tumor tissue is well known in CRC. In genome-wide scale, we explored whether differential methylation is associated with MSI status. Methods: We carried out a genome-wide methylation assay (Illumina 450K) for a total of 250 paired samples from 125 CRC patients (m = 72, f = 53) at different stages (stage1:25, stage II: 33 and stageIII: 67). Of them 101 had left-sided (descending colon to rectum) CRC and 30 had MSI, and 34 had somatic mutation in KRAS (rs112445441). Results: MSI was more frequent in the right-sided tumor (54% vs. 17%, p = 0.003). Frequency of KRAS mutation was not different between right and left-sided CRC (29% vs. 27%). Among the patients with microsatellite stable (MSS) CRC (n = 95), paired comparison of methylation data between tumor and corresponding normal tissue revealed a total of 1641 tumor-specific differentially methylated loci (DML) covering 686 genes that were significant at FDR 0.001 and the magnitude of difference (delta beta) was at least 20%; Similar analysis in patients with MSI (n = 30) revealed 6209 tumor-specific DML covering 2316 genes. This suggested that MSI is associated with methylation change in much larger number of genes. We could not find any methylation signature from normal colon tissue that could predict MSI or KRAS mutation in the corresponding tumor tissue. However, we identified 413 genes to be differentially methylated in tumor tissue compared to corresponding normal tissue only in presence of MSI, irrespective of KRAS mutation status, tumor staging, and location of tumor. These are “MSI-associated tumor-specific genes”. Among these, 19 DML covering17 genes showed delta-beta >30%. The list was enriched in genes associated with biologically relevant GO-terms like, “negative regulation of cell proliferation”, “regulation of MAP kinase activity”, “regulation of biological process” etc. We also identified 240 genes differentially methylated in tumor tissue compared to corresponding normal tissue irrespective of MSI status, KRAS mutation, tumor staging, and location of tumor. These are “general tumor-specific genes”. Among these loci, 87 DML (49 genes) showed delta-beta >30%. Conclusions: Our study shows evidence of association between MSI and DNA methylation in the pathogenesis of CRC. Citation Format: Muhammad G. Kibriya, Mohammed Kamal, Mustafizur Rahman, Shantanu Roy, Maruf Raza, Rupash Paul, Habibul Ahsan, Zahidul Haq, Farzana Jasmine. Interaction of Microsatellite Instability (MSI) and tumor for Differential DNA Methylation in Colorectal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2778.