Numerical abnormalities of chromosome 9 and p16CDKN2A gene deletion detected by FISH in non-small cell lung cancer.

BACKGROUND: Lung cancer is one of the most common types of cancer worldwide and its pathogenesis is closely associated with various environmental exposures and gene alterations. The identification of genetic changes is a useful strategy toward understanding tumourigenesis and specific genetic associations. Since the tumor suppressor gene p16 located at 9p21 chromosomal region might have an important role in lung carcinogenesis, the aim of the present study was to investigate p16 gene alterations and numerical aberrations of chromosome 9 in non-small cell lung cancer. MATERIALS AND METHODS: Nineteen cases of non-small cell lung cancer (11 squamous cell carcinomas, 6 adenocarcinomas and 2 large cell carcinomas) were investigated by fluorescence in situ hybridization (FISH) technique using a DNA p16 probe and alpha-satellite probe specific for chromosome 9. RESULTS: Polysomy 9 was found in 13 cases (6/11 squamous cell carcinomas, 5/6 adenocarcinomas and 2/2 large cell carcinomas). p16 gene alterations were found in 16 cases. Among them, deletion of p16 gene was found in 15 cases (8/11 squamous cell carcinomas, 5/6 adenocarcinomas and 2/2 large cell carcinomas). In six cases with p16 gene deletion, homozygous deletion was observed. CONCLUSION: Numerical aberrations of chromosome 9 and p16 gene deletion are common findings in all subtypes of non-small cell lung cancer. Despite suggesting the p16 gene in the 9p chromosomal region plays a role in lung carcinogenesis, the presence of other oncogenes reflected by polysomy 9 participating in the neoplastic process cannot be excluded. Data of the present study also suggest, that there might not be a fundamental relationship between genetic changes and histological subtype of non-small cell lung cancer.

Is aneusomy of chromosome 9 alone a valid biomarker for urinary bladder cancer screening?

BACKGROUND: Detection of genetically-changed tumor cells in the urine is one of the new approaches for the screening of bladder carcinomas. In a previous study, numerical aberrations of chromosome 9 were found in 85.18% of bladder tumors studied by the fluorescence in situ hybridization (FISH) technique. The purpose of the present study was to investigate whether chromosome 9 aneusomy alone is a valid, cost effective, biomarker for bladder cancer screening. MATERIALS AND METHODS: Twenty-seven voided urine specimens obtained from 22 bladder cancer patients, either at initial diagnosis or at the follow-up, were analyzed by the FISH technique with the centromeric probe specific for chromosome 9. RESULTS: In all except 2 out of the 13 specimens with a histological confirmation of cancer, FISH analysis showed aneusomy 9 (sensitivity 84.61%). Among 6 cases with a negative cystoscopy but a positive FISH analysis, 3 recurred within the following 2 months, while 2 no-recurrent patients continued to show positive FISH findings after 6 months. One patient was considered to be false-positive. Four cases with a negative cystoscopy showed disomy 9 and 2 of them recurred. CONCLUSION: Aneusomy 9 has a high sensitivity (84.61%) for the detection of bladder cancer. Patients with a negative cystoscopy but with aneusomy 9 should be kept under close clinical surveillance for potential disease recurrence. However, negative FISH results might not be a negative predictor for disease recurrence. Our results encourage further studies with a large number of patients and a long-term follow-up with concurrent FISH analysis.

Numerical aberrations of chromosomes 9 and 11 detected by FISH in Greek bladder cancer patients.

BACKGROUND: Bladder cancer is a genetically heterogeneous disease. The chromosomal aberrations observed are non-random and they are often correlated with disease progression. Several environmental risk factors have also been reported to be implicated in the pathogenesis of this disease. The aim of this study was to evaluate, by FISH technique, the numerical aberrations of chromosomes 9 and 11 in Greek bladder cancer patients and to correlate them with grade and histological stage of the tumors. MATERIALS AND METHODS: FISH with a-satellite DNA probes specific for chromosomes 9 and 11 were applied to 35 primary bladder tumors directly processed for cytogenetic study. RESULTS: Numerical aberrations of chromosome 9 were observed in 23 out of 27 tumors (85.18%). Monosomy 9 was detected in 12 cases (44.45%) and polysomy in 11 cases (40.74%). Statistical analysis showed that polysomy 9 was linked to histological stage (p = 0.024) and grade (p = 0.01) of the tumors, while monosomy 9 was correlated with tumor stage (p = 0.050). Numerical aberrations of chromosome 11 were observed in 25 out of 35 cases (71.43%). Polysomy was detected in 24 cases (68.57%), while only one case (2.86%) had monosomy 11. Polysomy 11 was found mainly in high-grade and advanced-stage tumors. CONCLUSION: Numerical aberrations of chromosome 9 could be a potential biomarker for bladder cancer screening. Further studies must be carried out to investigate gene alterations reflected by numerical aberrations of chromosomes 9 and 11 also contributing to the classification of this disease.