Genetic imbalances in pT2 breast cancers of southern Chinese women

doi:10.1016/S0165-4608(00)00328-9

Cancer Genetics and Cytogenetics

Volume 124, Issue 1, 1 January 2001, Pages 56-61

https://doi.org/10.1016/S0165-4608(00)00328-9 Get rights and content

Abstract

While much information has been reported on the genetic alterations in breast cancers of Caucasians, little is known about the Oriental populations where breast cancers currently rank the second most common neoplasm. As a first step toward understanding the underlying genetics changes in this population, we used comparative genomic hybridization (CGH) to the genome-wide analysis of forty pT2 tumors from patients of a racially homogenous population in southern China. A complex pattern of genetic alterations emerged with the commonest chromosomal gains identified on 1q (58%), 8q (55%), 11q13 (25%), 16p (28%), 17q (53%) and 20q (35%), and frequent losses on 8p (38%), 11q (28%), 13q (30%) and 18q (25%). When breast cancers with and without lymph-node metastasis were compared, a higher copy gain of 10p was identified in the node-positive group (P=.036). An overall increase in the average number of genetic aberrations was also identified in the late onset group (>45 years)(P=.042) with a higher incidence of genetic losses noted (P=.035). In particular, losses on 16q were detected in 30% of the late onset patients but none in the early onsets (P=0.049). In this study, we have illustrated the pattern of genetic changes in breast tumors of southern Chinese females. While frequent 1q, 8q, 17q and 20q gains, and common 8p and 13q deletions detected were consistent to those aberrations reported from the Caucasian populations, the difference in genetic changes associated in lymph-node metastasis and age of onset identified should provide the basis for additional investigations into the underlying tumorigenesis in the Oriental population.

Introduction

Breast cancer is the second most common cause of cancer mortality among southern Chinese women [1]. Although the incidence of breast cancer in Chinese women is currently only about one-half of that found in the Caucasians, there has been a three-fold increase in occurrence over the last decade. This rapidly rising incidence will soon reach the epidemic proportion seen in the West. While breast cancers in the West have been extensively studied, information on the underlying genetic alterations in Chinese has been scarce. We, therefore, undertook a genome-wide analysis on breast tumors of southern Chinese women with the aim to understanding the pattern of genetic alterations. The technique of comparative genomic hybridization (CGH), which enables the identification of genetic aberrations in the entire tumor genome, was used to the study of 40 primary breast tumors. As secondary aberrations accumulate during tumour progression, we have confined our analysis to a group of small stage pT2 primary tumors, so that a correlation with metastasis-related events, as well as a comparison between early and late onset cancers, could be carried out. Recurring aberrations identified were also compared to those reported from the West.

Section snippets

Patients

Frozen tumor tissues were collected from 40 southern Chinese patients (aged 32–85 years; 10 early onset tumors from patients aged ⩽45 years) who underwent surgical resection with curative intent. Fifteen patients had lymph node metastasis at presentation. All primary tumors were ⩽5 cm in diameter on pathology examination, except for case BC22 being 6 cm. Most tumors were infiltrating ductal carcinoma, apart for 3 lobular and 1 medullary type (Table 1).

Comparative genomic hybridization

The CGH hybridization of differentially

Results and discussion

In the 40 primary breast tumors analyzed, frequent chromosomal gains were identified on 1q (58%), 8q (55%), 11q13 (25%), 16p (28%), 17q (53%) and 20q (35%), and recurring losses on 8p (38%), 11q (28%), 13q (30%) and 18q (25%) Fig. 1, Fig. 2. These findings were broadly compatible to those studies reported from Europe and the United States where non-random chromosomal aberrations of 1q, 8q, 17q and 20q13 copy number gains, and recurrent losses of 13q, 8p, 17p and 16q have been indicated 4, 5, 6,

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Original articlesGenetic imbalances in pT2 breast cancers of southern Chinese women

Abstract

Introduction

Section snippets

Patients

Comparative genomic hybridization

Results and discussion

Am J Pathol

Am J Pathol

Eur J Cancer

The potential impact of breast cancer screening in Hong Kong

Aust N Z J Surg

Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors

Science

Molecular cytogenetics of primary breast cancer by CGH

Genes Chrom Cancer

Comparative genomic hybridization of ductal carcinoma in situ of the breastidentification of regions of DNA amplification and deletion in common with invasive breast carcinoma

Oncogene

Genetic alterations in primary breast cancers and their metastasesdirect comparison using modified comparative genomic hybridization

Genes Chrom Cancer

Genetic laterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histological type

Br J Cancer

DNA copy number amplifications in human neoplasms; review of comparative genomic hybridization studies

Am J Pathol

Genetic changes in breast cancer detected by comparative genomic hybridization

Int J Cancer

Distinct somatic genetic changes associated with tumor progression in carrier of BRCA1 and BRCA2 germ-line mutations

Cancer Res

Genetic alterations in ERBB2- amplified breast carcinomas

Clin Cancer Res

New genes potentially involved in breast cancer metastasis

Anticancer Res

Expression of MUC1 gene product in mucinous carcinoma of the breastcomparison with invasive ductal carcinoma

Acta Histochem Cytochem

Genetic alterations in breast cancer

Genes Chrom Cancer

Inhibition of c-myc expression by phosphorothioate antisense oligonucleotide identifies a critical role for c-myc in the growth of human breast cancer

Cancer Res

Original articles
Genetic imbalances in pT2 breast cancers of southern Chinese women