Allelic loss in chromosomal region 1q21–23 in breast cancer is associated with peritumoral angiolymphatic invasion and extensive intraductal component

doi:10.1053/ejso.1999.0921

European Journal of Surgical Oncology (EJSO)

Volume 26, Issue 5, August 2000, Pages 455-460

https://doi.org/10.1053/ejso.1999.0921 Get rights and content

Abstract

Aims: Breast cancer is the most frequent cancer in the female population and the involvement of chromosomal alterations is often implicated in the development of cancer. The aim of our study was to assess loss of heterozygosity (LOH) in chromosome 1 in relation to clinical and pathological parameters. Methods: Tumours, corresponding normal tissues and peripheral blood samples from 50 women with operable breast cancer, were analysed by polymerase chain reaction (PCR) at 16 polymorphic DNA markers, on both the long and short arm of chromosome 1. Results: There was a significant correlation between chromosomal region 1q21–23 and the presence of extensive intraductal component (EIC) and peritumoral angiolymphatic (PALI) invasion, both independent markers of local recurrence. Conclusions: Allelic loss in region 1q21–23 may be a valuable prognostic biological marker for the detection of local relapse in breast cancer, in combination with other histological and clinical parameters.

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Our previous work has shown that a number of genes locating on 1q21 were down-regulated in esophageal squamous cell carcinomas (ESCC) and they may involve in carcinogenesis. To determine whether chromosome 1q LOH occurs in ESCC, we analyzed LOH in 61 ESCCs using 18 microsatellite markers on chromosome 1q. Forty-six of 61 (75.4%) tumors presented LOH at one or more loci. A significant association was found between chromosome 1q LOH and histopathological grade. LOH on D1S3466 had a negative correlation with family history, whereas LOH on D1S2777 positively correlated with smoking. These results suggest this region harbor putative tumor suppressor gene(s) contributing to tumorigenesis and differentiation in ESCC.
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Citation Excerpt :
The analysis of such data is further complicated by the widely varying criteria used to declare LOH. For example, in electrophoretic allele typing, a decrease in allele intensity of at least 50% in tumor versus normal DNA has been used (Gaki et al. 2000), as has a difference in the allele intensity ratio of ⩾20% (Kollias et al. 2000). Such quantitative distinctions belie the certainty with which LOH is often described.
Somatic loss of heterozygosity (LOH) has been widely reported in breast cancer as a means of identifying putative tumor-suppressor genes. However, individual studies have rarely spanned more than a single chromosome, and the varying criteria used to declare LOH complicate efforts to formally differentiate regions of consistent versus sporadic (random) loss. We report here the compilation of an extensive database from 151 published LOH studies of breast cancer, with summary data from >15,000 tumors and primary allelotypes from >4,300 tumors. Allelic loss was evaluated at 1,168 marker loci, with large variation in the density of informative observations across the genome. Using studies in which primary allelotype information was available, we employed a likelihood-based approach with a formal chromosomal instability and selection model. The approach seeks direct evidence for preferential loss at each locus compared with nearby loci, accounts for heterogeneity across studies, and enables the direct comparison of candidate regions across the genome. Striking preferential loss was observed (in descending order of significance) in specific regions of chromosomes 7q, 16q, 13q, 17p, 8p, 21q, 3p, 18q, 2q, and 19p, as well as other regions, in many cases coinciding with previously identified candidate genes or known fragile sites. Many of these observations were not possible from any single LOH study, and our results suggest that many previously reported LOH results are not systematic or reproducible. Our approach provides a comparative framework for further investigation of regions exhibiting LOH and identifies broad genomic regions for which there exist few data.
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Breast cancer is the most prevalent cancer type in women and allelic loss constitutes one of the commonest genetic alterations in mammary neoplasias. Frequent detection of Loss of Heterozygosity indicates genes with putative tumour suppressor activity in breast carcinomas. Imbalance between two alleles might also be related with increased expression of an oncogene within a locus. Loci exhibiting frequent allelic loss in breast cancer have been detected, spread throughout the genome, and may contain genes with potential significance in breast carcinogenesis. Loss of Heterozygosity patterns in breast cancer give evidence for multiple clonality of the disease, and that accumulation of such lesions is probably implicated in disease development. Studies on deletions of known breast cancer genes suggest interactions with other common genetic events during disease initiation and progression. Allelic loss has been repeatedly associated with adverse characteristics and poor outcome in breast neoplasms. Detection of allelic loss in the serum of breast cancer patients and in premalignant breast lesions could herald the potential for diagnosis of the disease at an early, and thus curable, stage.
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^f1: Correspondence to: Professor D. A. Spandidos, Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete. Tel/Fax: +031081394633; E-mail: [email protected]

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Original ArticleAllelic loss in chromosomal region 1q21–23 in breast cancer is associated with peritumoral angiolymphatic invasion and extensive intraductal component

Abstract

Biochem Biophys Acta

Bioch Bioph Res Commun

Lancet

Eur J Cancer

Clonal chromosome abnormalities in human breast carcinomas. I. Twenty-eight cases with primary disease

Genes Chromosom Cancer

1p13 is the most frequently involved band in structural chromosomal rearrangements in human breast cancer

Genese Chromosom Cancer

Allelic loss on chromosome 1p is associated with progression and lymph node metastasis of primary breast carcinoma

Cancer

Chromosome 1 alterations in breast cancer: Allelic loss is related to lymphogenic metastases and poor prognosis

Genes Chromosom Cancer

Deletion mapping on chromosome 1p in well-differentiated gastric cancer

Br J Cancer

Deletion mapping defines different regions in 1p34.2 that may harbor genetic information related to human colorectal cancer

Oncogene

Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas

Cancer Res

Accumulations of genetic changes during development and progression of hepatocellular carcinoma: loss of heterozygosity of chromosome arm 1p occurs at an early stage of hepatocarcinogenesis

Genes Chromosom Cancer

Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma

Cancer Res

Significance of chromosome 1p loss of heterozygosity in neuroblastoma

Cancer Res

Allelotype of squamous cell carcinoma of head and neck: fractional allelic loss correlates with survival

Br Cancer

Allelic imbalance and instability of microsatellite loci on chromosome 1p in human non-small-cell lung cancer

Br J Cancer

Loss of heterozygosity identifies multiple sites of allelic deletions on chromosome 1 in human male germ cell tumors

Cancer Res

Original Article
Allelic loss in chromosomal region 1q21–23 in breast cancer is associated with peritumoral angiolymphatic invasion and extensive intraductal component