Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

Boynton, Robert F.; Blount, Patricia L.; Yin, Jing; Brown, Victoria; Huang, Ying; Tong, Yi; McDaniel, Tim; Newkirk, Carnell; Resau, James H.; Raskind, Wendy H.; Haggitt, Rodger C.; Reid, Brian J.; Meltzer, Stephen J.

doi:10.1073/pnas.89.8.3385

Cited by 186 publications

(102 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two RB polymorphisms were used to evaluate for LOH, a VNTR in intron 20 of RB (Yandell et al, 1989) and a BamHI RFLP in intron 1 (Bookstein et al, 1990). Ampli®cation using the polymerase chain reaction (PCR) was performed with primers and PCR conditions as previously described for these polymorphisms (Boynton et al, 1991;Bookstein et al, 1990). Denaturated PCR fragments from the VNTR were resolved on a 6% polyacrylamide-urea sequencing gel and autoradiogaphed.…”

Section: Loh At the Rb Locusmentioning

confidence: 99%

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

et al. 1997

View full text Add to dashboard Cite

Inactivation of the retinoblastoma protein (pRB) by mutations or abnormal phosphorylation is a mechanism by which tumour cells can subdue normal growth control. Among molecules involved in control of pRB phosphorylation, cyclin D1 and E have been found to be deregulated and overexpressed in various types of cancers. In order to study the cell cycle regulatory mechanisms in breast cancer, we have analysed the protein expression of cyclin D1 and E in 114 tumour specimens from patients with primary breast cancer using Western blotting. Twenty-®ve out of 34 tumours with overexpression of cyclin E showed uniform low cyclin D1 expression, and by immunohistochemical analysis of pRB we present evidence for the existence of pRB defects in approximately 40% of these tumours in contrast to no pRB defects in the other group of tumours. This result was supported by a high protein expression of the cyclindependent kinase inhibitor p16 in 44% of the tumours with high cyclin E and low D1 expression, and all immunohistochemical pRB defect tumours showed a high p16 protein level. Additionally, an abnormal low pRB phosphorylation in relation to a high proliferative activity and loss of heterozygosity of the retinoblastoma susceptibility gene locus were found in all but one tumour with immunohistochemical defect pRB. Interestingly, tumours with high cyclin E and low D1 expression were generally oestrogen receptor negative suggesting a role for cell cycle regulators in the mechanisms leading to oestrogen independent tumour growth. Furthermore, the prognosis di ered markedly for the patients in the various groups of tumours, indicating that the heterogeneous nature of breast cancer pathogenesis and the clinical course in part could be explained by di erent and distinctive sets of cell cycle defects.

show abstract

Section: Loh At the Rb Locusmentioning

confidence: 99%

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Mutated APC has also been reported in a range of sporadic tumours, including pancreatic and gastric tumours and the majority of adenomas and carcinomas of the colorectum Horii et al, 1992;Nakatsuru et al, 1992). Furthermore, loss of heterozygosity at 5q21 has been observed in sporadic tumours of the breast and oesophagus (Boynton et al, 1992;Thompson et al, 1993;Kashiwaba et al, 1994).…”

Section: Introductionmentioning

confidence: 98%

Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice

Kongkanuntn¹,

Bubb²,

Sansom³

et al. 1999

Oncogene

View full text Add to dashboard Cite

We have analysed the pattern of b-catenin expression by immunohistochemistry in mice singly or multiply mutant for Apc, p53 and Msh2. We observed increased expression of b-catenin in all intestinal lesions arising on an Apc Min +/7 background. In all categories of lesion studied mosaic patterns of b-catenin expression were observed, with the proportion of cells showing enhanced expression decreasing with increasing lesion size. p53 status did not alter these patterns. We also show that bcatenin dysregulation marks pancreatic abnormalities occurring in Apc Min +/7 and (Apc Min +/7, p537/7) mice. In these mice both adenomas and adenocarcinomas of the pancreas arose and were characterized by increased expression of b-catenin. We have extended these analyses to intestinal lesions arising in mice mutant for the mismatch repair gene Msh2. In these mice, increased expression of b-catenin was again observed. However, in contrast with Apc Min +/7 mice, a subset of lesions retained normal expression. Taken together, these ®ndings show that increased expression of b-catenin is an e cient marker of early neoplastic change in both murine intestine and pancreas in Apc mutant mice. However, we also show that dysregulation of b-catenin is not an obligate step in the development of intestinal lesions, and therefore that genetic events other than the loss of Apc function may initiate the transition from normal to neoplastic epithelium.

show abstract

“…Our ability to screen multiple loci in flow-sorted material has been limited by the number of cells, often less than 104, available for study. To determine whether PEP could be used to extend our ability to investigate somatic genetic lesions in these small samples we have used constitutive and tumor samples that had been evaluated previously with polymorphic markers using standard PCR techniques (1,7,8,12) to address five main criteria: (i) the appearance of LOH artifacts at low template concentration; (ii) the detection of multiple loci in a single sample; (iii) the effect of normal cell 'contamination' on the detection of LOH; (iv) the use of different classes of polymorphic markers; (v) the detection of alleles in samples from multiple patients.…”

Section: Discussionmentioning

confidence: 99%

“…DNA content cell sorting was used to isolate diploid populations and aneuploid populations from patients whose constitutive and tumor samples had been evaluated previously with polymorphic markers using standard PCR techniques (1,7,8,12). DNA was extracted from each sample by our standard protocol (11) PEP and locus-specific PCR analyses Stock DNA samples from the diploid and the aneuploid samples were serially diluted in ddH20 for the concentrations used in the PEP reactions.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Genotypic analysis of multiple loci in somatic cells by whole genome amplification

Barrett¹,

Reid

Joslyn³

1995

Nucl Acids Res

View full text Add to dashboard Cite

To screen multiple loci in small purified samples of diploid and aneuploid cells a PCR-based technique of whole genome amplification was adapted to the study of somatic lesions. DNA samples from different numbers of flow-sorted diploid and aneuploid cells from biopsies were amplified with a degenerate 15mer primer. Aliquots of these reactions were then used in locus-specific reactions using a single round of PCR cycles with individual sets of primers representing polymorphic markers for different regions. As a result, polymorphic markers for different chromosomal regions, including VNTRs and dinucleotide repeats, can be used to perform up to 30 locus-specific PCR assays with a single sample obtained from fewer than 1000 cells.

show abstract

Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

Cited by 186 publications

References 30 publications

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice

Genotypic analysis of multiple loci in somatic cells by whole genome amplification

Contact Info

Product

Resources

About