Poster 7: A Genetic Progression Model for Head and Neck Cancer: Implications for Field Cancerization

Califano, Joseph A.; Clayman, Gary L.; Sidransky, David; Koch, Wayne M.; Piantadosi, Steven; Riet, Peter Vander; Nawroz, Homaira; Westra, William H.; Corio, Russell L.

doi:10.1016/s0194-5998(96)80631-0

Cited by 674 publications

(951 citation statements)

References 6 publications

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“…Allelotype studies in other tumour types have suggested that chromosome lOq harbours at least one gene that is important in the tumour progression of meningioma, prostate cancer and brain tumours (von Deimling et al, 1992;Rempel et al, 1993;Gray et al, 1995). As chromosome lOq loss was the second most frequent finding in SCLC after 3p deletions, which are implicated in early tumour development (Bockmuhl et al, 1996;Califano et al, 1996), we speculated that this lesion may contribute particularly to the highly malignant phenotype of SCLC and other types of human lung carcinomas.…”

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confidence: 90%

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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confidence: 90%

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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“…These early p53 alterations have been more frequently observed in patients suffering from multiple cancers compared to those with only one tumor (Waridel et al, 1997;Homann et al, 2001), in agreement with the field model . In cytogenetic studies, allelic imbalances/loss of heterozygosity (LOH) and chromosomal aneuploidy have been detected in tumors and mucosal biopsies of tumor patients (Soder et al, 1995;Bedi et al, 1996;Califano et al, 1996;Ai et al, 1999;Partridge et al, 2000;Braakhuis et al, 2002;Tabor et al, 2004). Chromosomal aneuploidy appears to precede malignant transformation as indicated by findings of monosomy and trisomy in histologically normal squamous mucosa (Ai et al, 2001;Wolf et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer

et al. 2006

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“…The first model suggested for HNSCC combines, as an early event, multiple LOH with allelic loss at 9p, 3p, 17q, 4q and 13q. LOH at 18q and 8p are considered late genetic events (Califano et al, 1996). On the basis of already published cytogentic data, two main genetic pathways in HNSCC were suggested (Höglund et al, 2001) by using the two principal components of genomic imbalance (gains and losses): one with À1p, À1q and À7q as an early event followed by À8p and À4p, and another starting with þ 7q, and subsequently followed by þ 11pq, þ 8q and þ 1pq.…”

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confidence: 99%

Impairment of MLH1 and CDKN2A in oncogenesis of laryngeal cancer

et al. 2004

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Our study aimed at elucidating which genetic alterations tend to form a network and could be applied as molecular markers of larynx squamous cell carcinoma (LSCC). A panel of genes involved in tumorigenesis was investigated. To search for the possible mechanisms of gene silencing, loss of heterozygosity (LOH) was analysed followed by testing DNA methylation and protein expression for those genes found with the highest frequency of LOH (CDKN2A (55.4%), MLH1 (46.0%), RB1 (35.7%)). A correlation of both LOH and hypermethylation with the loss of expression for CDKN2A and MLH1 was found. Disrupted Rb pathway (loss of expression of RB1 and/or of CDKN2A) in 55.9% of analysed cases confirmed the hypothesis that RB1 pathway is altered in head and neck squamous cell carcinomas, with CDKN2A (45%), rather than RB1 (11.8%) being more frequently inactivated. In LSCC, LOH tends to occur together in gene pairs or triplets. The pair MLH1/CDKN2A and triplets MLH1/TSG on 8p22/CDKN2A and MLH1/ CDKN2A/RB1 are related to staging and grading. LOH in MLH1 correlates with lower and LOH in CDKN2A with higher grades of LSCC. It can be concluded that MLH1 and CDKN2A play an important role in LSCC development and progression.

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Poster 7: A Genetic Progression Model for Head and Neck Cancer: Implications for Field Cancerization

Cited by 674 publications

References 6 publications

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

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

Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer

Impairment of MLH1 and CDKN2A in oncogenesis of laryngeal cancer

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