Frequent loss of heterozygosity for markers on chromosome arm 10q in chondrosarcomas

Raskind, Wendy H.; Conrad, Ernest U.; Matsushita, Mark

doi:10.1002/(sici)1098-2264(199606)16:2<138::aid-gcc8>3.0.co;2-0

Cited by 29 publications

(18 citation statements)

References 48 publications

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“…More recently Frayling et al 13 using a more centromeric marker (D10S220) showed frequent LOH (37%) in sporadic colorectal adenocarcinomas on 10q11-21 suggesting the presence of a tumour suppressor gene (TSG) in this region. The presence of a TSG in this region is supported by findings in other tumour types including renal, 14 chondrosarcomas 15 and malignant glioma 3 that have shown frequent LOH at 10q11-21.…”

supporting

confidence: 52%

Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma

Fawole

Simpson

Ramesh

et al. 2002

Intl Journal of Cancer

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Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p ‫؍‬ 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference Key words: chromosome 10q; LOH; sporadic colorectal adenocarcinoma; TSG; tumor progressionColorectal adenocarcinoma is the second most common cause of cancer related death in the Western world. The majority of colorectal cancers are considered sporadic and present in the 7th and 8th decades of life, whereas hereditary colorectal adenocarcinoma accounts for approximately 10% of all cases and usually presents before the age of 50 years. 1 The initiation and progression of sporadic colorectal tumors has been described as a multi-step etiology involving the progressive loss of tumour suppressor function and concomitant inappropriate oncogene activation resulting in the deregulation of controlled cellular proliferation. 2 Frequent loss of heterozygosity (LOH) has been shown in regions harboring known tumour suppressor genes including 5q21(APC), 17p13(p53) and 18q21(DCC) involved in the development of sporadic colorectal adenocarcinoma. 2 Studies have shown frequent LOH on chromosome 10q in several tumour types including malignant gliomas, 3 malignant melanomas, 4 prostate, 5,6 endometrial, 7 breast 8,9 and bladder cancer. 10 Early studies of this chromosome, however, showed infrequent loss in colorectal cancer. 11 A subsequent allelotyping study 12 of sporadic colorectal adenocarcinomas showed that LOH on chromosome 10q was an infrequent event, however, this study only investigated a single locus (10q25-26). More recently Frayling et al. 13 using a more centromeric marker (D10S220) showed frequent LOH (37%) in sporadic colorectal adenocarcinomas on 10q11-21 suggesting the presence of a tumour suppressor gene (TSG) in this region. The presence of a TSG in this region is supported by findings in other tumour types including renal, 14 chondrosarcomas 15 and malignant glioma 3 that have shown frequent LOH at 10q11-21.Recently a TSG called PTEN, MMAC1 or TEP1 16 -18 has been localized to the chromosomal loci 10q23.3, loss and concomitant mutation in the retained PTEN allele have been shown in glioblastomas, 19 malignant melanoma, 20,21 squamous cell lung carcino...

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supporting

confidence: 52%

Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma

Fawole

Simpson

Ramesh

et al. 2002

Intl Journal of Cancer

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“…56 Chromosome 10 frequently demonstrates LOH in chondrosarcoma, especially at 10q11.2. 57 On the other hand the presence of two copies of certain chromosomes may be essential for growth of transformed cells. In the 29 near-haploid solid tumors retrieved from the literature, chromosome 7 is present in disomic state in 67% of near-haploid solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Near-Haploidy and Subsequent Polyploidization Characterize the Progression of Peripheral Chondrosarcoma

Bovée

Royen

Bardoel

et al. 2000

The American Journal of Pathology

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Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of osteochondroma (peripheral chondrosarcoma). We previously used DNA flow cytometry to demonstrate that near-haploidy is relatively frequent in peripheral chondrosarcomas. We performed fluorescence in situ hybridization (FISH) to interphase nuclei using centromeric probes, a genome wide loss of heterozygosity (LOH) analysis, and comparative genomic hybridization on five peripheral chondrosarcomas. We demonstrated near-haploidy in two low-grade tumors with only one copy and LOH of most chromosomes. Few chromosomes are disomic, with retention of heterozygosity and overrepresentation at comparative genomic hybridization. One tumor contains both a near-haploid clone with chromosomes in monosomic and disomic state, and an exactly duplicated clone. Two high-grade tumors clearly demonstrate polyploidization because most chromosomes show LOH and two copies at FISH, whereas few chromosomes have four copies with retention of heterozygosity. Using DNA from a relative, we demonstrate that chromosome loss is random regardless of parental origin. Using FISH on paraffin slides, we exclude near-haploidy to result from meiosis-like division in binucleated cells, characteristic for chondrosarcoma. In conclusion, our results indicate that near-haploidy characterizes the progression from osteochondroma toward low-grade chondrosarcoma. Moreover, further progression toward high-grade chondrosarcoma is characterized by polyploidization. Chondrosarcoma, the second most common primary malignant bone tumor after osteosarcoma, is a malignant cartilage-forming tumor occurring predominantly in adults. The majority of chondrosarcomas develops de novo and is located centrally within the medullary cavity (central chondrosarcoma). In contrast, ϳ15% arise within the cartilage cap of a long-standing osteochondroma (peripheral chondrosarcoma), mostly in patients suffering from the hereditary multiple exostoses syndrome. Hereditary multiple exostoses syndrome is a familial disorder with an autosomal dominant mode of inheritance.1-4 Malignant transformation is estimated to occur in 1 to 5% of osteochondromas.The development of peripheral chondrosarcoma results in genetic instability characterized by a high percentage of loss of heterozygosity (LOH) and a wide variation in DNA ploidy.5 LOH in peripheral chondrosarcoma most frequently involves the TP53 (80%), RB1 (71%), and EXT1 (65%) loci. 5 In contrast, peridiploidy and a low percentage of LOH in central tumors indicates that a different oncogenic molecular mechanism may be operative. 5 We have detected hypodiploidy, which is uncommon for human solid tumors, in 29% of peripheral chondrosarcomas and not in central chondrosarcomas.5 Others mention hypodiploidy in 8 to 31% of chondrosarcomas without further subclassification.6 -9 Near-haploidy, which is a very rare phenomenon in human solid tumors in general, is found especially in low-grade peripheral chon...

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“…Frequent LOH on chromosome 10 has been reported in a variety of cancers, including glioma, glioblastoma multiforme, prostate cancer, endometrial cancer, chondrosarcoma, bladder cancer, malignant melanoma, and follicular thyroid tumors (Knowles et al, 1994;Gray et al, 1995;Fults and Pedone, 1993;Ittmann, 1996;Trybus et al, 1996;Lacombe et al, 1996;Rasheed et al, 1995;Raskind et al, 1996;Nagase et al, 1996;Zedenius et al, 1996;Isshiki et al, 1993). A limited number of studies have indicated the potential involvement of chromosome 10 in bladder cancer (Knowles et al, 1994;Kallioniemi et al, 1995;Wang et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer

et al. 1998

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Frequent loss of heterozygosity for markers on chromosome arm 10q in chondrosarcomas

Cited by 29 publications

References 48 publications

Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma

Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma

Near-Haploidy and Subsequent Polyploidization Characterize the Progression of Peripheral Chondrosarcoma

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer

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