Heritable colorectal cancer and cancer genes: Systemic expressions

Kopelovich, Levy

doi:10.1002/mc.2940080104

Cited by 14 publications

(14 citation statements)

References 43 publications

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“…This observation would also be consistent with twin studies that indicate "a very high proportion and perhaps a majority of breast cancers arise in a susceptible minority of women" (30). The abnormal growth behavior of SF in cancer-prone individuals has suggested that at least in some cases cancer can be considered a systemic disease (10,46), and that this difference in the behavior of SF cells from such individuals may be a practical basis for prevention, diagnosis, and management of the disease.…”

Section: Discussionsupporting

confidence: 83%

Saturation Density of Skin Fibroblasts as a Quantitative Screen for Human Cancer Susceptibility

Rubin

2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Genomic analysis of human cancers reveals a large number of genetic changes per cell that presumably underlie development of the disease. The complexity of these changes that differ from one type of cancer to the other and from patient to patient with the same type of cancer raises questions about the feasibility of genomic analysis as an indicator of susceptibility to cancer. However, skin fibroblasts (SF) from individuals in families with heritable forms of cancer, and from cancer-bearing individuals, show correlation with a significant increase in saturation density (SD), as well as other neoplasia-related properties. Procedures are described for amplifying and quantifying differences in SD on the basis of studies of spontaneous transformation in the NIH 3T3 line of mouse fibroblasts. It is proposed that such procedures be evaluated as quantitative screens for susceptibility to cancer in the general population. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2366-72)

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Section: Discussionsupporting

confidence: 83%

Saturation Density of Skin Fibroblasts as a Quantitative Screen for Human Cancer Susceptibility

Rubin

2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In this regard, earlier studies originally based on "the ubiquitous fibroblast" 27 that was used as a surrogate for the cells of tumor origin indicated a systemic presence of some of these biomarkers, including their occurrence in heritable cancers and in the corresponding sporadic cancers. 28 Based on the early discoveries of these biomarkers, a flowchart of events that define the initiated state at the cellular/phenotypic level and its relationship to cancer predisposition in the autosomal dominant cancer syndrome has been proposed. 20,28 The clinical relevance of alterations at the "one-hit" level to the cancer process is highlighted by the fact that essentially 80-100% of patients with a heritable cancer syndrome will develop cancer, 6 indicating that observations in phenotypically normal cells/tissues from these individuals are directly associated with actual cancer development.…”

Section: O Ver 100 Years Ago (1902-1914) Theodor Boveri Suggested a Rmentioning

confidence: 99%

“…28 Based on the early discoveries of these biomarkers, a flowchart of events that define the initiated state at the cellular/phenotypic level and its relationship to cancer predisposition in the autosomal dominant cancer syndrome has been proposed. 20,28 The clinical relevance of alterations at the "one-hit" level to the cancer process is highlighted by the fact that essentially 80-100% of patients with a heritable cancer syndrome will develop cancer, 6 indicating that observations in phenotypically normal cells/tissues from these individuals are directly associated with actual cancer development. These results have also led us to formulate a distinction between the autosomal and recessive forms of heritable cancer, wherein genetic information in the former at the cellular level is associated with cancer initiation, whereas genetic information at the cellular level in the latter is presumably consistent with the early phases of cancer promotion.…”

Section: O Ver 100 Years Ago (1902-1914) Theodor Boveri Suggested a Rmentioning

confidence: 99%

“…These results have also led us to formulate a distinction between the autosomal and recessive forms of heritable cancer, wherein genetic information in the former at the cellular level is associated with cancer initiation, whereas genetic information at the cellular level in the latter is presumably consistent with the early phases of cancer promotion. 28 In this regard, developmental abnormalities that are concordant with increased cancer risk in some of the dominantly heritable cancer syndromes, 6 may at some level provide further insights about the development of specific cancers.…”

Section: O Ver 100 Years Ago (1902-1914) Theodor Boveri Suggested a Rmentioning

confidence: 99%

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Heritable one-hit events defining cancer prevention?

Kopelovich

Herbert

2013

Cell Cycle

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“…Other hereditary cancer syndromes with reported one-hit effects include familial adenomatous polyposis involving heterozygosity for APC germ-line mutations (17)(18)(19)(20), tuberous sclerosis gene family, and von Hippel-Lindau disease (21). The common conclusion of all these studies is that heterozygosity for a mutant tumor suppressor gene alters the expression profile of normal colonic and other epithelial cells.…”

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confidence: 99%

One-Hit Effects and Cancer

Iniesta¹,

Chien²,

Wicha³

et al. 2010

Cancer Prevention Research

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This perspective on Bellacosa et al. (beginning on p. 48 in this issue of the journal) discusses the important biology of microscopically normal tissues in carriers of germ-line BRCA1 or BRCA2 mutations. The work of Bellacosa et al. is an important step toward discerning which pathways may be altered when one BRCA allele is inactivated. Cancer Prev Res; 3(1); 12-5. ©2010 AACR.Breast cancer is the most common lethal cancer experienced by women in developed countries, affecting one in eight women during her lifetime. U.S. estimates for 2009 include 192,370 new diagnoses of and ∼40,170 deaths from breast cancer (1). Although many factors are implicated in the initial steps of breast cancer development, a significant family history is the most important factor after gender and age. Despite the discovery of multiple breast cancer susceptibility tumor suppressor genes, such as BRCA1, BRCA2, PTEN, TP53, CDH1, CHEK2, and PALB2, only ∼15% of the number of cases in familial clusters of breast cancer can be explained by strongly or moderately penetrant single-locus susceptibility genes. Therefore, large numbers of familial cases of breast cancer remain unexplained, presenting a challenge for practitioners attempting to counsel family history patients in cancer genetics clinics.An estimated 5% to 10% of all breast cancers arise in the setting of inherited mutations in BRCA1 or BRCA2 and are presumed to be the result of these factors (2). Mutations in either of these genes occur in <50% of families with evidence of possible autosomal transmission of inherited susceptibility (3). Discovered nearly 15 years ago, germ-line mutations in the BRCA1 and BRCA2 genes in women (4-6) confer a breast cancer risk that is 10-to 20-fold higher than the risk of women without these mutations. BRCA1 and BRCA2 mutation carriers also have an increased risk for ovarian cancer and, to a mild degree, for gastrointestinal, prostate, pancreatic, and male breast cancers. At age 70, the risks of breast and ovarian cancer are 57% and 40%, respectively, for BRCA1 mutation carriers compared with 49% and 18%, respectively, for BRCA2 mutation carriers (7). BRCA1 and BRCA2 play an important role in double-strand break repair through the homologous recombination pathway and are considered to be tumor suppressor genes.The first description of oncogenic alterations to tumor suppressor genes came more than 40 years ago from Alfred Knudson, who based the description on epidemiologic studies of retinoblastoma. Knudson postulated that multiple damaging events in DNA (called "hits") are necessary to cause retinoblastoma. Children diagnosed with inherited retinoblastoma carry the first oncogenic event as an inherited or de novo germ-line mutation in RB, called the "first" hit. The second DNA injury could affect any somatic cell and would be acquired. If this second "hit" affected the wild-type allele of the locus, it could rapidly lead to cancer because both copies of the normal RB tumor suppressor gene would be lost. In contrast, nonhereditary retinoblasto...

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Heritable colorectal cancer and cancer genes: Systemic expressions

Cited by 14 publications

References 43 publications

Saturation Density of Skin Fibroblasts as a Quantitative Screen for Human Cancer Susceptibility

Saturation Density of Skin Fibroblasts as a Quantitative Screen for Human Cancer Susceptibility

Heritable one-hit events defining cancer prevention?

One-Hit Effects and Cancer

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