Characterization of Extensive Genetic Alterations in Ductal Carcinoma In Situ by Fluorescence In Situ Hybridization and Molecular Analysis

Murphy, Danielp .; Hoare, Stacey F.; Going, James J.; Ea, Mallon; George, W.D.; Kaye, SB; Brown, Robert; Black, D; Keith, W. Nicol

doi:10.1093/jnci/87.22.1694

Cited by 59 publications

(45 citation statements)

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“…Our results are consistent with previous studies, revealing increased copy numbers on chromosomal arm 10p in breast cancer (Ried et al, 1995;James et al, 1997;Murphy et al, 1995).…”

Section: Tpl-2 Gene Ampli®cation In Human Breast Tumourssupporting

confidence: 94%

Overexpression of the Tpl-2/Cot oncogene in human breast cancer

1999

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“…Our results are consistent with previous studies, revealing increased copy numbers on chromosomal arm 10p in breast cancer (Ried et al, 1995;James et al, 1997;Murphy et al, 1995).…”

Section: Tpl-2 Gene Ampli®cation In Human Breast Tumourssupporting

confidence: 94%

Overexpression of the Tpl-2/Cot oncogene in human breast cancer

1999

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“…Therefore, in order to quantitate hTR copy number, a group of tumours showing high quality hybridisations and good morphology were selected for further study using previously established criteria (Murphy et al, 1995a). From Table 1 it can be seen that of 18 SCC-HN biopsies, 17 showed subpopulations of nuclei (ranging from 18 ± 90%), with more than two hybridisation sites for hTR per nucleus.…”

Section: Copy Number Gains Of the Htr Locus In Solid Tumoursmentioning

confidence: 99%

“…Of 12 cervix biopsies, all contained subpopulations of nuclei (ranging from 14 ± 84%) with greater than two hybridisation sites for hTR per nucleus. The range in number of hTR signals per nucleus in each tumour also varied, and although some of this variation is likely to be due to nuclear truncation (Murphy et al, 1995a) nuclei with up to a maximum of 10 copies of hTR were detected (Table 1).…”

Section: Copy Number Gains Of the Htr Locus In Solid Tumoursmentioning

confidence: 99%

“…For each sample, the mean hTR copy number per nucleus, the % of nuclei within each biopsy with more than two hybridization sites, (%42), and the minimum and maximum number of hybridization sites per nucleus, are shown. More than 10% of the nuclei had to show greater than two signals for the hTR probe, to be evaluated as having a gain of hTR sequences, (Murphy et al, 1995a) Figure 2 Gains in hTR copy number in cervix cancers and squamous cell carcinomas of the head and neck (SCC-HN). The ratio for hTR copy number to chromosome 3 centromericsequence copy number is shown for 18 SCC-HN biopsies and 12 cervix biopsies.…”

Section: Copy Number Gains Of the Htr Locus In Solid Tumoursmentioning

confidence: 99%

“…Probe labelling, in situ hybridisation and probe detection were as previously described (Murphy et al, 1995a;Soder et al, 1995) using the Hybaid Omnislide system (Hybaid Ltd, Teddington, UK). Chromosome 3-speci®c centromeric probes were purchased from Appligene-Oncor (Durham, UK) and Cytocell Ltd (Banbury, UK).…”

Section: Fish Analysismentioning

confidence: 99%

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Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer

et al. 1997

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Telomere length is maintained by the enzyme, telomerase, which has been linked to cellular immortality and tumour progression. However, the reasons for the high levels of telomerase found in human tumours are unknown. We have mapped the human telomerase RNA gene, (hTR), to chromosome 3q26.3 and show the hTR gene to be ampli®ed in four carcinomas, (2/33 cervix, 1/31 head and neck, 1/9 lung). In addition, increased copy numbers of the hTR locus was also observed in 97% of tumours. By in situ hybridisation, the histological distribution of high levels of hTR expression could be demonstrated in a lung tumour and its metastasis with hTR ampli®cation. These results are the ®rst report of genetic alterations involving a known component of telomerase in human cancer. Indeed, it is also the ®rst report of the ampli®cation of a speci®c locus within the chromosome 3q region frequently subject to copy number gains in human tumours. In addition, we also show for the ®rst time the histological distribution of the RNA component of telomerase in human tumours.

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In Situ hybridization and its diagnostic applications in pathology

1997

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In situ hybridization (ISH) is a technique by which specific nucleotide sequences are identified in cells or tissue sections. These may be endogenous, bacterial or viral, DNA or RNA. On the basis of research applications, the technique is now being translated into diagnostic practice, mainly in the areas of gene expression, infection and interphase cytogenetics. Diagnostic applications are most often based on short nucleotide sequences (oligomers) labelled with non‐isotopic reporter molecules, and sites of binding may be localized by histochemical or immunohistochemical methods. The technique can be applied to routinely fixed and processed tissues; with some targets, it is even possible to obtain hybridization in autopsy material. ISH has been used to detect messenger RNA (mRNA) as a marker of gene expression, where levels of protein storage are low; for example, to confirm an endocrine tumour as the source of excess hormone production. Its application in infectious diseases has to date been mainly in viral infections, such as the typing of human papillomavirus (HPV) or the detection of Epstein–Barr virus by the presence of small nuclear RNAs (EBERs). The expression of mRNAs for histone proteins has been used to detect cells in S phase, and related methods may be applied to detect apoptotic cells. Using probes to chromosome‐specific sequences, it is possible to detect aneuploidy, and to document changes in specific chromosomes, which may have prognostic significance in some tumours, such as B‐cell chronic lymphatic leukaemia. Using sequence‐specific probes, translocations can be identified, such as the t(11;12) of Ewing's sarcoma. This review presents an outline of the technique of in situ hybridization and discusses areas of current and potential diagnostic application. © 1997 John Wiley & Sons, Ltd.

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Characterization of Extensive Genetic Alterations in Ductal Carcinoma In Situ by Fluorescence In Situ Hybridization and Molecular Analysis

Abstract: This approach may give direction to future research aimed at precisely mapping loci altered in DCIS and help in understanding the biologic events associated with tumor progression or recurrence.

Cited by 59 publications

References 0 publications

Overexpression of the Tpl-2/Cot oncogene in human breast cancer

Overexpression of the Tpl-2/Cot oncogene in human breast cancer

Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer

In Situ hybridization and its diagnostic applications in pathology

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