Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p

Petersen, Iver; Langreck, Holger; Wolf, Guenter; Schwendel, Anke; Psille, R.; Vogt, Peter H.; Reichel, Martin; Ried, Thomas; Dietel, Manfred

doi:10.1038/bjc.1997.13

Cited by 174 publications

(143 citation statements)

References 39 publications

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“…In agreement with the current body of literature, deletions of DNA were frequently identified at 3p, 5q, 10q, 16q and 17p with gains of DNA frequently found on 1p, 3q and 14q. 5 Several genes within these regions have been investigated further in SCLC including the tumour suppressor genes fhit (3p), APC and MCC (5q), PTEN (10q) and p53 (17p). The formation of 5p iso-chromosomes was suggested by the M-FISH karyotypes in 2 of the cell lines and this was confirmed by high-level gains of the entire p arm of chromosome 5 by CGH analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Whang-Penn et al 4 first described this consistent chromosomal abnormality in SCLC cell lines by conventional karyotyping and subsequent comparative genomic hybridization (CGH) and loss of heterozygosity analysis of SCLC tumours have confirmed the prevalence of chromosome 3p abnormalities. 5,6 Three distinct regions of loss have been identified at 3p21.3, 3p12 and 3p25, suggesting the presence of multiple tumour suppressor gene on chromosome 3. 7 Several putative tumour suppressor genes have been characterised within these regions of loss however, to date, the RASSF1A gene at 3p21.3 is the only gene to be positively associated with lung cancer tumourigenesis.…”

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confidence: 99%

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Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Ashman

Brigham

Cowen

et al. 2002

Intl Journal of Cancer

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Small cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G-banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M-FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M-FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Ashman

Brigham

Cowen

et al. 2002

Intl Journal of Cancer

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“…The comparison between the deletion pattems of gliomas and those of lung carcinomas is intriguing. Similar to glioblastomas, SCLC generally exhibit deletions of the entire chromosome or chromosomal arm (Levin et al, 1994;Ried et al, 1994;Petersen et al, 1997a), whereas SCC and astrocytoma are more frequently characterized by interstitial deletions (Rasheed et al, 1995). Both, astrocytoma and SCC may progress to glioblastoma and SCLC lOq loss in lung cancer 275 respectively (Churg et al, 1980;Kleihues et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Allelic loss on chromosome 10q in human lung cancer: association with tumour progression and metastatic phenotype

Petersen

Wolf²,

Bockmühl³

et al. 1998

Br J Cancer

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Summary We analysed 78 carcinomas of the lung for allelic losses on chromosome 1 Oq. The tumours were of different stage and grade and comprised 22 small-cell lung carcinomas (SCLC), 40 squamous cell carcinomas (SCC), 11 adenocarcinomas, four large-cell carcinomas and one carcinoid. They were investigated by six polymorphic markers located between 1 0q21 and 1 Oqter. We observed a high incidence of loss of heterozygosity (LOH) in SCLC (91%) and metastatic SCC (56%). Non-metastatic SCC showed deletions in three cases (14%) and no LOH was found in the other types of non-small-cell lung cancer. The statistical analysis indicated that the presence of LOH correlated significantly with advanced tumour stages in the entire collective and in particular within the SCLC and SCC subgroups. For SCC, a positive association was found between LOH and metastases formation, while in SCLC the number of non-metastatic tumours was too small for a final conclusion. Whereas SCLC was frequently characterized by multiple allelic losses, suggesting the deletion of the entire chromosomal arm, SCC showed interstitial imbalances. A high incidence of allelic loss was observed between the markers D10S677 and D10S1223. The analysis of five informative cases suggested the presence of two non-overlapping regions between the loci Dl 0S677/D10S1237 and Dl OS1213/Dl OS1223. In SCLC, we did not find mutations in the putative tumour-suppressor gene MXI1. The data indicate that LOH on chromosome 10q is associated with tumour progression in SCC and SCLC. Thus it may become a useful genetic marker in the assessment of the malignant potential of these tumour types.Keywords: small-cell lung cancer; squamous cell carcinomas of the lung; loss of heterozygosity; tumour genetics Cancer of the lung has the highest incidence of all solid tumours and is the leading cause of cancer deaths (Pisani et al, 1993). The major histopathological distinction of clinical relevance is between small-cell and non-small-cell lung carcinomas. SCLC has to be considered a systemic disease at the time of diagnosis as the majority of cases show early metastases formation. It is preferentially treated by chemotherapy and radiotherapy. The NSCLC consist mainly of three subtypes, i.e. adenocarcinomas, squamous cell carcinomas (SCC) and large-cell carcinomas (LCLC). The significance of the latter group is unclear as LCLC frequently show features of either adenocarcinomas or SCC; they can usually be attributed to these two subgroups by ultrastructural examination. There is a prevailing pattern of distribution within the lung. Whereas adenocarcinomas tend to be located in the periphery, SCC and SCLC arise preferentially from the central bronchi near the hilus.A distinct histopathological diagnosis with far-reaching clinical consequences, i.e. possibly curative operation vs palliative chemotherapy, is often complicated by the morphological heterogeneity that occurs in up to 30% of cases (Muller and FisselerEckhoff, 1989). The tumour heterogeneity is reflected in the World Health Organiza...

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“…In addition to these known hotspots of chromosomal copy number changes in prostatic adenocarcinoma, a novel region of chromosomal loss on 4q could be detected in our subset of cases. Deletions on 4q are frequent events in other tumour entities such as lung tumours (Petersen et al, 1997), renal carcinoma (Jiang et al, 1998), papillary bladder cancer (Simon et al, 1998), and appear to play a crucial role during aggressive progression of hepatocellular carcinoma (Piao et al, 1998). It is postulated that several, yet unidentified, putative tumour suppressor genes may be located on 4q (Hammoud et al, 1996).…”

Section: Tumour Progression In Prostate Cancer 205mentioning

confidence: 99%

Chromosomal changes during development and progression of prostate adenocarcinomas

Zitzelsberger

Engert²,

Walch

et al. 2001

Br J Cancer

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Summary Chromosomal copy number changes were investigated in 16 prostate carcinomas, 12 prostatic intraepithelial neoplasias (PIN; 4 low-grade and 8 high-grade) adjacent to the invasive tumour areas, and 5 regional lymph node metastases. For this purpose, comparative genomic hybridization (CGH) was performed and a copy number karyotype for each histomorphological entity was created. CGH on microdissected cells from non-neoplastic glands was carried out on 3 different cases to demonstrate the reliability of the overall procedure. None of the non-neoplastic tissue samples revealed chromosome copy number changes. In PIN areas, chromosomal imbalances were detected on chromosomes 7, 8q, Xq (gains), and on 4q, 5q, 8p, 13q and 18q (losses). In the primary tumours, recurrent (at least 25% of cases) gains on chromosomes 12q and 15q, and losses on 2q, 4q, 5q, Xq, 13q and 18q became apparent. Losses on 8p and 6q as well as gains on 8q and of chromosome 7 were also detected at lower frequencies than previously reported. The pooled CGH data from the primary carcinomas revealed a novel region of chromosomal loss on 4q which is also frequently affected in other tumour entities like oesophageal adenocarcinomas and is supposed to harbour a new tumour suppressor gene. Gains on chromosome 9q and of chromosome 16 and loss on chromosome 13q were observed as common aberrations in metastases and primary tumours. These CGH results indicate an accumulation of chromosomal imbalances during the PIN-carcinoma-metastasis sequence and an early origin of tumour-specific aberrations in PIN areas.

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Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p

Cited by 174 publications

References 39 publications

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Allelic loss on chromosome 10q in human lung cancer: association with tumour progression and metastatic phenotype

Chromosomal changes during development and progression of prostate adenocarcinomas

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