Trisomy 8 in leukemia: A GCRI experience.

Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005–September 2008). Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML) (36), acute myeloid leukemia (AML) (17), and acute lymphoblastic leukemia (ALL) (7). In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22), t(15;17), and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered.

Utility of urinary biomarkers in oral cancer.

OBJECTIVE: Oral cancer is the leading malignancy in India, with tobacco playing a major role in the etiology. The aim of the present study was to quantify nitrate+nitrite (NO2+NO3) in tobacco products as well as to study tobacco exposure related biomarkers in controls, patients with oral precancers (OPC) and oral cancer patients. MATERIALS & METHODS: Healthy individuals (n=90) were grouped into without habit of tobacco (NHT, n=30) and healthy individuals with habit of tobacco (WHT, n=60). Oral cancer patients with a tobacco habit were classified into abstinence (n=62) and non-abstinence (n=64) groups according to status at the study time. Urinary nicotine and cotinine levels were analyzed by modified high-pressure liquid chromatography (HPLC) using a UV detector. Levels of NO2+NO3 in tobacco and urine, and urinary thioether levels were estimated by spectrophotometry. RESULTS: NO2+NO3 levels in different types of tobacco product ranged between 0.13 to 3.39 mg/g. The Odds Ratio (OR) analysis indicated positive associations of both smoking and chewing habits of tobacco with high risk of development of oral cancer. Urinary nicotine, cotinine and NO2+NO3 levels were significantly elevated in WHT, patients with OPC and oral cancer patients as compared with the NHT group. This was also the case for urinary thioether levels. Levels of urinary nicotine and cotinine were also higher in the non-abstinence group with oral cancers. CONCLUSION: The results confirmed that tobacco chewing and smoking habits are prominent risk factors for development of oral cancer in the western part of India (Gujarat). Urinary nicotine, cotinine, NO2+NO3 and thioether levels can be helpful for screening programs for oral cancer.

Loss of sex chromosome in acute myeloid leukemia.

Loss of sex chromosomes has been reported in normal and malignant marrows and its frequency increases with age in both situations. It is not clear whether the sex chromosome loss is a critical mutational event for neoplastic transformation or a genetic change related to ageing. The present study was undertaken to analyze incidence of loss of sex chromosomes in leukemia patients. Karyotypic analysis in bone marrow cells was carried out in total 270 AML patients registered at G.C.& R.I. during January 2000 to October 2003. Out of 270, 22 patients had loss of sex chromosome in addition to other disease specific chromosomal abnormalities. Out of 22 patients, 50% (11 of 22) were of the pediatric age (up to 14 years), and only 10% (3 of 22) patients were above the age of 50 years, maximum age being 65 years. On follow-up, only in patients with pathological remission normal 46XX/XY karyotypes were seen. Whereas in patients with persistent leukemic activity, clones with loss of sex chromosome were observed. The results indicate that sex chromosome loss in these cases may be equivalent of a clonal cytogenetic process rather than related to ageing process.

An Increased Incidence Of C-Band Heteromorphism In Hereditary Breast Cancer Patients and Their Healthy Blood Relatives An Indian Experience.

Healthy blood relatives (HBR) of the hereditary breast cancer (HBC) patients are considered to be at higher risk to develop cancer. However, all of them do not suffer from same. This may indicate the possibility of association with genetic polymorphism among them. We have studied this genetic polymorphism in terms of C-band heteromorphism among 11 HBC patients, 36 HBR and results were compared with 22 control females. Significantly higher incidence (p < 0.001) of C-band heteromorphism has been observed among the HBC patients and their HBR as compared to the control females. At the same time, however, the difference in incidence of C-band heteromorphism among HBC patients and their HBR were not statistically significant. The findings indicate possibilities of (i) an association between C-band heteromorphism and hereditary breast cancer, and (ii) C-band heteromorphism may be one of the important factors conferring HBR at an elevated risk to develop the breast cancer.

Constitutive Heterochromatin Polymorphism In Pediatric Cancer Patients.

Incidence of constitutive C-band heteromorphism (CBH) is reported to be higher in patients with malignancy by some studies, while in others no difference is reported between control and malignant conditions. We have studied incidence of CBH in pediatric cancer patients in terms of > 25% size difference between the homologues of chromosome #1, #9 and #16 and compared it with (i) age-matched controls, (ii) controls with minimum 60 years of age and (iii) parents/siblings of pediatric cancer patients and overall prevalence of CBH was comparable between patients and three groups of control subjects. Statistically significant difference was observed between the total lengths of C-band of chromosome #1 for pediatric cancer patients and first degree relatives group (p < 0.01). 17 families of pediatric cancer patients were studied for the pattern of CBH. In three patients, CBH analysis, more number of cancer families and normal pedigrees will be more informative. The problem still remains unresolved and should be analyzed qualitatively using techniques of molecular cytogenetics.