Nuclear Anomalies, Chromosomal Aberrations and Proliferation Rates in Cultured Lymphocytes of Head and Neck Cancer Patients

Alex George,Vikas Bhuria,Shouvik Banerjee,Radha Saraswathy,Sivakumar Ethirajan,Rupraj Dey,Ashok Siluvaimuthu

doi:10.7314/apjcp.2014.15.3.1119

Alex George, Vikas Bhuria + Show 5 more

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https://doi.org/10.7314/apjcp.2014.15.3.1119

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Abstract

Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANEUP) in patients (CSAs, 0.0294±0.0038; CTAs, 0.0925±0.0060; DICs, 0.0213±0.0028; and CANEUPs, 0.0308±0.0035) compared to controls (CSAs, 0.0005±0.0003; CTAs, 0.0058±0.0015; DICs, 0.0005±0.0003; and CANEUPs, 0.0052±0.0013) where p<0.001. Similarly, spontaneous nuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, 0.01867±0.00108; NPBs, 0.01561±0.00234; NBUDs, 0.00658±0.00068) compared with controls (MNi, 0.00027±0.00009; NPBs, 0.00002±0.00002; NBUDs, 0.00011±0.00007).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients (1.525±0.005552) compared to healthy subjects (1.686±0.009520 ) (p<0.0001). In conclusion, our preliminary results showed that visible spontaneous genomic instability and low rate proliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

Highlights

Head and neck cancers (HNC) are placed fifth among the common cancers occurring worldwide
Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis
We examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls

Summary

Introduction

Head and neck cancers (HNC) are placed fifth among the common cancers occurring worldwide. Over 200,000 cases of head and neck cancers occur each year in India and nearly 80,000 oral cancers are diagnosed every year. HNC constitute an anatomically heterogeneous group of cancers These arise from all mucosal sites within the head and neck, primarily the oral cavity, oropharynx, hypopharynx, larynx and nasopharynx. The squamous cell carcinogenesis has a progressive nature of genetic abnormalities triggered by mutational changes occurred by the risk factors or genetic predisposition in the genes regulating cell cycle progression (Weinstain, 2000). This multistep carcinogenesis is a permanent suffering and lethal if left untreated in the initial stages. Why does everyone not develop cancer? Most HNC cases and deaths are due to both individual predispositions linked to certain genetic characteristics and synergetic effect of exposure to carcinogens caused by life style behaviors: like

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