Clonal origin of human tumors

Fialkow, Philip J.

doi:10.1016/0304-419x(76)90003-2

Cited by 298 publications

(170 citation statements)

References 91 publications

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“…3,4 Alternatively, the monoclonal theory is that proliferation may spread through the mucosa or lymphatics to form multiple neoplasms derived from a common progenitor cell. 1,2 In previous studies, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced multifocal lesions in a bladder contained heterogeneous p53 mutations, conforming with the concept of field carcinogenesis. 38 In addition, molecular evidence for field carcinogenesis has been studied extensively using molecular markers such as p53 and K-ras mutations, loss of heterozygosity, and X-chromosome inactivation analysis in lung carcinoma, 39 pancreas carcinoma 40 and skin carcinoma.…”

Section: Discussionmentioning

confidence: 58%

“…The monoclonal theory postulates that cells from a single neoplastic cell may spread to produce multiple tumors sequentially. 1,2 In contrast, the field carcinogenesis theory postulates that an area of tissue simultaneously becomes genomically unstable and predisposed to neoplasia due to prolonged exposure to carcinogens, resulting in multiple tumors. 3,4 According to the latter theory, the entire esophageal epithelial surface, or "field", is exposed to repeated carcinogenic insults, and multiple epithelial tumors can arise independently from multifocal precancerous lesions, which may develop and progress at different rates.…”

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confidence: 99%

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p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis

Ito

Ohga

Saeki

et al. 2004

Intl Journal of Cancer

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Inactivation of the p53 tumor suppressor gene is one of the most frequent genetic alterations observed in human esophageal carcinomas. In patients with esophageal carcinoma, one of the significant pathological features of the tumor is the presence of multiple lesions within the esophagus. However, the molecular mechanisms involved in the occurrence of multiple lesions have remained elusive. To characterize p53 alterations in multiple esophageal carcinomas and to study their roles in carcinogenesis, we performed p53 immunohistochemical and p53 mutation analyses using laser capture microdissection on surgically resected human esophageal carcinomas from 11 patients: 9 patients with multiple esophageal carcinomas, 1 with an intramural metastasis lesion within the esophagus and 1 with an intraepithelial carcinoma lesion contiguous to the main lesion. In each of the patients with multiple esophageal carcinomas, we examined samples from 1 main lesion and 1 representative concomitant lesion. Molecular analyses of samples from fresh-frozen normal tissues and tumor tissues of the main lesion (whole tumor) were also performed by the same method. p53 protein accumulation was observed in 16 (72.7%) of 22 lesions from the 11 cases. No p53 mutation was found in normal esophageal tissues. In the 9 cases of multiple esophageal carcinomas, point mutations were detected in the whole tumor in 1 (11.1%) case, in the microdissected tumor samples of main lesions in 3 (33.3%) cases and in the microdissected tumor samples of concomitant lesions in 3 (33.3%) cases. For the microdissected tumor samples, there was a 54.5% (12/22) concordance rate between the results of immunostaining and molecular analysis. In the 8 cases of whole tumors in which a p53 mutation was not observed, 2 cases revealed p53 mutation in the microdissected tumor samples of the main lesion. All 6 cases of multiple esophageal carcinomas that showed a p53 mutation in the microdissected tumor sample had a discordant p53 mutational status between the main and concomitant lesions. In contrast, both the intramural metastasis lesion and the intraepithelial carcinoma contiguous to the main lesion showed p53 mutational patterns identical to those of the main lesions. In conclusion, the analysis of microdissected DNA by laser capture microdissection is useful for characterizing the heterogeneity of the p53 gene mutation in multiple carcinoma lesions that cannot be accurately analyzed in whole esophageal tumor DNA. The finding of different p53 gene mutations among multiple esophageal carcinoma lesions suggest further evidence of multicentric or field carcinogenesis of the human esophagus.

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Section: Discussionmentioning

confidence: 58%

mentioning

confidence: 99%

p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis

Ito

Ohga

Saeki

et al. 2004

Intl Journal of Cancer

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“…This is an approach we are considering for further study of our case. Monoclonal X-chromosome inactivation is not always indicative of monoclonal origin of a tumor, i.e., neoplasia (32). Predominance of a single clone of cells, from a polyclonal or multicellular origin can give rise to a monoclonal pattern.…”

Section: Discussionmentioning

confidence: 99%

Erdheim-Chester Disease: Case Report, PCR-Based Analysis of Clonality, and Review of Literature

et al. 2002

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Erdheim-Chester disease (ECD) is a rare, distinct clinicopathologic entity with nearly pathognomonic radiographic features. The lesions consist of lipidstoring CD68 (؉), CD1a (؊) non-Langerhans' cell histiocytes, either localized to the bone or involving multiple organ systems in the body. Whether these histiocytic proliferations represent monoclonal neoplastic populations or are part of a polyclonal reactive process is unclear. We present a case report of ECD in a 35-year-old African-American woman with a progressive course over 6 years. We investigated the clonality of the histiocytes using the HU-MARA assay on paraffin-embedded tissue sections but did not find any evidence that these cells represent a monoclonal population. In this report, the characteristics of ECD are reviewed, the genetic basis of the HUMARA assay is discussed, and our results in the context of other clonality investigations reported in the literature to date are summarized.

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“…In direct studies of human tumor clonality, early work focused on tissue derived from black females heterozygous for the G6PD A variant. These studies examined differences in electrophoretic patterns of G6PD A and B proteins extracted from tissue samples (1). Given the admixture of cells constituting a tumor (tumor cells, vessels, stromal elements, and inflammatory cells), it was not surprising that such tumors were commonly demonstrated to be polyclonal.…”

Section: Discussionmentioning

confidence: 99%

X-inactivation patch size in human female tissue confounds the assessment of tumor clonality

Novelli

Cossu

Oukrif

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

116

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Most models of tumorigenesis assume that tumors are monoclonal in origin. This conclusion is based largely on studies using X chromosome-linked markers in females. One important factor, often ignored in such studies, is the distribution of X-inactivated cells in tissues. Because lyonization occurs early in development, many of the progeny of a single embryonic stem cell are grouped together in the adult, forming patches. As polyclonality can be demonstrated only at the borders of X-inactivation patches, the patch size is crucial in determining the chance of demonstrating polyclonality and hence the number of tumors that need to be examined to exclude polyclonality. Previously studies using Xlinked genes such as glucose-6-phosphate dehydrogenase have been handicapped by the need to destroy the tissues to study the haplotypes of glucose-6-phosphate dehydrogenase [Fialkow, P.-J.

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Clonal origin of human tumors

Cited by 298 publications

References 91 publications

p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis

p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis

Erdheim-Chester Disease: Case Report, PCR-Based Analysis of Clonality, and Review of Literature

X-inactivation patch size in human female tissue confounds the assessment of tumor clonality

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