Clinical and pathological associations with allelic loss in colorectal carcinoma [corrected]

Kern, Scott E.; Fearon, Eric R.; Tersmette, Kasper W. F.; Enterline, John P.; Leppert, M.; Nakamura, Yūichi; White, Ralph de Vere; Vogelstein, Bert; Hamilton, SR

doi:10.1001/jama.261.21.3099

Cited by 188 publications

(87 citation statements)

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“…The study group consisted of 46 carcinomas that were previously investigated for loss of heterozygosity at 5q, 17p and 18q (Kern et al, 1989), activating point mutations in ras oncogenes (Kern et al, 1989) and DNA ploidy al., 1993;DiGiuseppe et al, 1994). In our study group, 19 of the 46 colorectal carcinomas (41%) showed inactivating mutations in the p53 gene.…”

Section: Discussionmentioning

confidence: 99%

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma

Slebos

Baas²,

Clement³

et al. 1996

Br J Cancer

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Section: Discussionmentioning

confidence: 99%

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma

Slebos

Baas²,

Clement³

et al. 1996

Br J Cancer

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“…This conclusion, which is derived from numerous studies that used varying techniques (microsatellite analysis, CGH, CGH array, SNP array, karyotyping), is actually consistent with the observation that 18q loss is also associated with distant metastasis. 40 As indicated in Table 1, 24,26 the loss of 8p 24,34 -39,41 or 17p (the location of TP53 tumor suppressor gene) 33,34,42 is also linked to lower survival rate.…”

Section: Somatic Copy Number Aberrations In Crcsmentioning

confidence: 99%

Gene Dysregulations Driven by Somatic Copy Number Aberrations-Biological and Clinical Implications in Colon Tumors

Bacolod

Barany

2010

The Journal of Molecular Diagnostics

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The majority of colorectal cancer (CRC) cases have chromosomal instability , in which the tumor genome is characterized by gross chromosomal aberrations such as gains in 20q , 13q , 8q , and 7 , and losses in 4, 8p , 18q , and 17p. These somatic copy number changes (gains , losses , and somatic uniparental disomies) are crucial to CRC progression as they drive genes toward cancer-promoting (oncogenic or tumor suppressive) states. Numerous studies have shown that the loss of 18q or 8p is associated with poorer clinical outcome in CRCs. Either chromosomal arm may contain a tumor suppressor gene (or genes), whose deactivation by copy loss (loss of wild-type allele , decreased expression) can be crucial to the later stages of cancer progression. Our own integrated genomic analysis (single nucleotide polymorphism array , expression array) of more than 200 CRC tumor and normal samples indicates that the overall down-regulation of genes within the 8p or 18q arm is associated with lower survival rate. Among the often down-regulated , poor prognosis-associated 8p genes is MTUS1, whose gene product (a mitotic spindleassociated protein) was recently demonstrated to have a tumor suppressive property. Within 18q is ATP5A1 , which codes for the catalytic a component of mitochondrial H ؉ -ATP synthase. Like SMAD4(also in 18q) , the decreased expression of ATP5A1 appears to be a marker of unfavorable clinical outcome in

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“…This heterogeneity is probably responsible for the failure of otherwise effective therapeutic strategies (Heppner and Miller, 1998;Leith and Dexter, 1986;Vinyals et al, 1999). It is assumed that a correlation exists between increased genomic damage and malignant behavior (Arribas et al, 1997;Kern et al, 1989). Different molecular approaches have been used to quantify the extent of genomic disruption along the tumor and its association with identifiable clinical manifestations.…”

Section: Discussionmentioning

confidence: 99%

“…Different molecular approaches have been used to quantify the extent of genomic disruption along the tumor and its association with identifiable clinical manifestations. Increased levels of chromosomal imbalances throughout the genome (Arribas et al, 1997;Kern et al, 1989;Offerhaus et al, 1992) and deregulation of gene expression (Tortola et al, 1999b) are associated with tumor aggressiveness in human colorectal cancer. However, the technical complexity of these approaches precludes their routine application.…”

Section: Discussionmentioning

confidence: 99%

“…The observed correlation between increased chromosomal instability and malignant behavior (Arribas et al, 1997;Kern et al, 1989), also seen in the present study as assessed by AI, might reflect two opposite situations: (i) that, in a given tumor, cells harboring the most abnormal karyotype are the most invasive and are selected for during distal dissemination (Duesberg et al, 1998;Lengauer et al, 1997); or (ii) that the presence of aneuploid clones is a symptom of the global chromosomal instability of the tumor, the more abnormal tumor cells are not necessarily viable (Scott et al, 1988). The aneuploidy profile of the primary tumor is often reproduced in its corresponding metastases, as found in unpublished observations (RA Risques and MA Peinado), and by Tollenaar et al (1997).…”

Section: Discussionmentioning

confidence: 99%

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Redefining the Significance of Aneuploidy in the Prognostic Assessment of Colorectal Cancer

Risques

Marcuello

Pétriz

et al. 2001

Laboratory Investigation

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SUMMARY:The aberrant content of DNA, or aneuploidy, is a hallmark of tumor cells and may be associated with malignant potential. Based on the hypothesis that aneuploidy, as a form of genetic instability, results in an increased capability to generate cell heterogeneity, we investigated whether a comprehensive assessment of aneuploidy extent and degree might be a reliable indicator of tumor aggressiveness. DNA content was determined by flow cytometry in the infiltrating front of 131 paraffinembedded primary colorectal carcinomas collected in a prospective design. Enrichment of tumor cells by sample microdissection resulted in neoplastic cell contents above 75%. An estimate of aneuploidy, the aneuploidy index (AI), was calculated as the tumor DNA content adjusted by the percentage of diploid and aneuploid cells in G0/G1. Thirty-nine tumors were diploid, 90 hyperdiploid, and 2 hypodiploid. The mean AI in aneuploid tumors was 1.20 Ϯ 0.17 and correlated with Dukes' stage and metastasis (p Ͻ 0.05). A high AI (receiver operating characteristic curve cutoff value greater than 1.14) predicted a poorer outcome in univariate (p ϭ 0.004) and multivariate (p ϭ 0.01) analyses. Based on these results, we postulate that aneuploidy is the molecular engine of progression in a subset of colorectal cancers, in which the AI seems to be a sensible and independent gauge of malignant potential. The AI determination may have prognostic application in colorectal cancer, especially in low-grade tumors, which might benefit from coadjuvant therapies. (Lab Invest 2001, 81:307-315).

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Clinical and pathological associations with allelic loss in colorectal carcinoma [corrected]

Cited by 188 publications

References 0 publications

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma

Gene Dysregulations Driven by Somatic Copy Number Aberrations-Biological and Clinical Implications in Colon Tumors

Redefining the Significance of Aneuploidy in the Prognostic Assessment of Colorectal Cancer

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