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Indian Journal of Human Genetics, Vol. 9, No. 1, Jan-Jun, 2003, pp. 10-12 Chromosomal Instability in peripheral blood lymphocytes in patients with malignancy Tulika Bose Department of Human Genetics, Andhra University, Visakhapatnam-530029, Andhra
Pradesh, India.
Code Number: hg03003 There are lot of studies on the cytogenetic changes in solid tumours but there are very few studies on the cytogenetic changes in peripheral blood by mphosytes in patients with malignancy. In the present study we evaluated peripheral blood lymphocyte cytogenetic changes on short term culture. Twenty four out of 250 patients with various malignancies showed some aberration of karyotypes in peripheral lymphocytes (9-6%) suggesting an underlying genetic instability in these cancer patients or alternatively demonstrating that these changes could be related to exposure to environmental mutagens. Key Words: Chromosomal immutability, Cancer cytogenetics, Acrocentric association, Anenploidy, Peripheral blood lymphocytes. INTRODUCTION Innumerable cytogenetic abnormalities have been described in both solid tumours and in various haematologivcal malignancies. This cytogenetic changes, which are non random have been clearly linked to certain areas of chromosome where genes for proto-oncogenes or tumour suppressor genes have been mapped.1,2 Though cancers arise out of somatic mutation through multihit processes yet one or more or the hits could have been inherited and may be the reason for multiple heritable neoplasms in cancer prone families. Some of the genes relating to hereditary predisposition of cancer are tumour suppressor genes like P53 gene, which is deleted or mutated in hereditary cancer syndromes like Li-Fraumeni Syndrome or as has also been described recently for familial breast cancers with BRCA1 or BRCA2 mutations. There is very little data available in English literature describing cytogenetics from peripheral blood lymphocytes in patients with cancers. Though in haematological malignancies like leukaemias or in disseminated lymphomas it is natural to pick up abnormal cytogenetics from peripheral blood lymphocytes. In the present study the cytogenetic changes form peripheral blood lymphocytes in a large cohort of various malignancies is being reported. MATERIAL AND METHODS Two hundred and fifty patients having various types of malignancies were selected for this study (Table 1). Detailed history of their exposure to various mutagens like Xrays, pesticides, working in chemical factories were taken. Peripheral blood lymphocytes culture from utilized a whole blood culture technique in RPMS-7640 media in presence of PHA (Phytohaemoglobin) using standard in vitro technique.3,4 Chromosome plates were classified using standard ISCN nomen cloture. Karyotypes were considered abnormal when they showed (a) Acrocentric associations (b) Premature centromeric division or (c) Aneuploidies. RESULTS The patients were aged between 9-72 years. 24 patients showed some chromosomal abnormalities out of 50 patients tested (48%). The differential distribution of the abnormalities in various groups of cancer patients presented in table 1. Six to 12% patients in each of the categories showed some abnormalities in peripheral blood lymphocyte cytogenetics out of six cervical cancer patients showing the cytogenetic abnormalities one had family history of other solid tumours and another patients had massive thyromegaly. All the six abnormality in these cases were either aneuploidy or polyploidy involving 9 to 17% of mitotic plates examined and involving only acrocentric chromosomes (Figure 1). Five breast cancer patients showed abnormalities in 11 -23% of mitotic plates. Two patients had family history of breast cancers involving more than one first degree relatives. One of the patients also had additional exposure to Xrays on several occasions for diagnostic purpose. Four acute lymphoblastic lenkaemiac and 3 non hodgkin lymphoma patients showed hyperploidy and except for residing in industrial areas they had no risk factors. Nine to 30% of their mitotic plates revealed these abnormalities. Patients presenting with oral cancers or throat cancers were relatively older, the youngest one was 40 years of age. All the 6 patients in this group with cytogenetic alteration showed premature centromeric division. Eleven to 27% of the mitotic plates showed such an abnormality. One of the patient worked in a chemical factory and the other one patient worked in shipyards where exposure to asbestos is a known hazard. DISCUSSION It is increasingly being realized that many cancers arise because of environmental exposure to mutagens. Some of our patients have been exposed to diagnostic Xrays, oral tobacco, and probably environmental mutagens because many of our patients lives in industrial areas. Quite a few of our breast cancer patients had strong family history. Though BRCA-1 & BRCA-2 mutations involving familial breast cancer patients have been worked out in western countries, no large scale studies have been under taken in this area from India. Considering the vast genetic heterogeneity in Indian population and known differences in breast cancer incidences in different Indian population, it is extremely important to see whether screening for BRCA1 & BRCA2 will be cost effective in early detection of breast cancer in much patients. Our study showed that around 10% of patients have abnormal cytogenetics from peripheral blood lymphocytes in untreated patients with various malignancies. Though the cytogenetic changes are quite nonspecific except in leukaemia / lymphomas where hyperploidy in associated with better prognosis yet this show an underlying genetic instability in patients with cancer. Aneuploidy involving acrocentric chromosomes are found more often in cancer patients. Premature division of centromere causes failure of attachment of mitotic spindle to separated and may be responsible for aneuploidy in some of these patients. One of the curious finding in the present study was demonstration of premature division of centromere only in oral / throat cancer patients. It is not known whether the predisposing factor like tobacco can cause this type of abnormality. One of the major argument against in the present study is that for solid tissue tumours why should we study peripheral blood lymphocytes? But as the result tends to show that indeed a proportion of patients with solid tumours show some evidence of chromosomal instability, further away form the site of tumour, suggesting that the inheritance of chromosomal instability through some of the genes involved in DNA repair and synthesis provided the proper background on which environmental mutagens causes the final damage or alternatively the changes also might indicate the effect of environmental mutagen in multiple tissues. ACKNOWLEDGEMENTS This paper was substantially re-edited. REFERENCES
Copyright 2003 - the Indian Society of Human Genetics The following images related to this document are available:Photo images[hg03003f1.jpg] [hg03003t1.jpg] |
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