Distinct patterns of genetic alterations in adenocarcinoma and squamous cell carcinoma of the lung
Introduction
Lung cancer is responsible for the highest cancer-related morbidity and mortality worldwide [1]. Non-small cell lung cancer (NSCLC) comprises approximately 80% of all lung cancers, among which adenocarcinoma (AdC) and squamous cell carcinoma (SqC) are now the two most common histological subtypes. Cigarette smoking continues to be an important aetiological factor, with a clear implication of involvement in over 95% of male cases [2]. A correlation between the incidence of lung cancer in females and smoking habit has also been observed in recent years [3].
Due to the high incidence and mortality rates, much effort has been drawn towards investigating the cause and course of NSCLC. Although classical cytogenetic studies by banding analysis can provide an overall view of structural and numerical abnormalities, the frequent presence of karyotypic complexity has precluded more accurate interpretation. Conversely, molecular characterisation by comparative genomic hybridisation (CGH) and allelotyping has shown common over-representations of 1q, 3q, 5p, 8q and 20, and loss of heterozygosity (LOH) on 3p, 8p, 13q and 17p in NSCLC 4, 5, 6. Despite the reportedly frequent genomic imbalances, the pattern of karyotypic alterations associated with AdC and SqC remains uncertain.
We have now conducted a comprehensive molecular cytogenetic characterisation of AdC and SqC tumours. By utilising CGH findings as a frame, individual information was examined in relation to chromosomal rearrangements described from spectral karyotyping (SKY). Cytogenetic information on NSCLC has mainly been derived from cell lines 7, 8, and we believe our study is the first to describe such information in primary tumours. Our combined CGH and SKY analysis shows distinct patterns of genetic aberration in the two specific NSCLC subtypes, which might in turn influence the different pathogenetic pathways adopted by these tumours.
Section snippets
Patients
Tumorous lung tissues were collected from 69 patients who underwent curative surgery for lung cancer at the Prince of Wales Hospital, Hong Kong. Tumours were classified according to the World Health Organisation histological typing of lung tumours, and staged according to the TNM classification of malignant tumours. 34 cases were diagnosed as AdC (age 43–79 years; stage T1–4N0–2M0–1) and 35 cases as SqC (age 47–83 years; stage T1–4N0–2M0). All patients had a smoking history. A smoker was
Results and discussion
CGH analysis of 69 NSCLC specimens produced informative findings in 61 (88%). In the series of SqC and AdC examined, genomic gains prevailed over losses (P<0.0005): a ratio of 10.1±5.6 copy gains ±(mean+S.D.) to 4.9±4.1 losses ±occurred in SqC, and a ratio of 6.2±5.1 copy gains ±to 2.2±1.8 losses in AdC. The aberrant tumour metaphases derived from SqC and AdC displayed a karyotype ranging from hyperdiploid to hypotetraploid. There was no significant difference in ploidy status between SqC and
Acknowledgements
This work was supported by a grant from the Research Grants Council of Hong Kong (Ref. No.: CUHK 4112/00M), and by The Kadoorie Charitable Foundations (under the auspices of the Hong Kong Cancer Genetics Research Group).
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