European multicenter study on LOH of APOC3 at 11q23 in 766 breast cancer patients: relation to clinical variables

Abstract

Loss of heterozygosity (LOH) for a specific chromosome region may indicate the presence of a tumour suppressor gene (TSG). Studies on tumour LOH have therefore been helpful to identify many TSGs (Bièche and Lidereau, 1995). High incidences of LOH of the 11q22-qter chromosome region have been seen in breast cancer (Hampton et al, 1994;Gudmundsson et al, 1995;Winqvist et al, 1995;Kerangueven et al, 1997;Laake et al, 1997) and also in several other human malignancies (Herbst et al, 1995;Rasio et al, 1995;Gabra et al, 1996;Hui et al, 1996). In addition, it has been shown that chromosome 11 can suppress tumorigenicity when transferred to breast cancer (Negrini et al, 1994;Phillips et al, 1996) and melanoma cell lines (Robertson et al, 1996).The distal half of chromosome 11q contains several genes indicated to be involved in tumorigenesis; e.g. ATM (the ataxia telangiectasia disorder gene at 11q23.1), DDX10 (a putative RNA helicase gene at 11q23.1), MLL1 (a gene at 11q23 frequently rearranged in acute leukaemia), LOH11CR2A (a potential tumour suppressor gene at 11q23) and CHEK1 (a gene at 11q24 encoding a protein kinase required for the DNA damage checkpoint function) (Ziemin-van der Poel et al, 1991;Savitsky et al, 1995Savitsky et al, , 1996Furnari et al, 1997;Monaco et al, 1997;Sanchez et al, 1997).LOH at 11q23 has been reported in association with poor postmetastatic survival in breast cancer (Winqvist et al, 1995). The crucial region of LOH seemed to map between loci D11S35 (11q22) and APOC3 (apolipoprotein C-3 at 11q23) (Hampton et al, 1994), in a chromosomal segment of less than 17 Mb (Arai et al, 1996). In the initial study of a Finnish breast cancer cohort, APOC3 appeared to be the most suitable marker for more careful examinations of the clinical effects of LOH of the 11q23 chromosomal region. Therefore, in the present European multicentrestudy, we analysed tumour and normal tissue pairs of 766 primary breast cancer patients from 11 countries to investigate the association between LOH at the APOC3 locus and clinical variables in greater detail. MATERIALS AND METHODSAltogether 766 primary tumour and normal tissue pairs from breast cancer patients were collected for the LOH analysis. The Summary High frequencies of loss of heterozygosity (LOH) in chromosome 11q22-qter have been observed in various malignancies, including breast cancer. Previous studies on breast carcinomas by Winqvist et al (Cancer Res 55: 2660-2664) have indicated that a survival factor gene is located in band 11q23, and that the highly informative microsatellite polymorphism at the APOC3 locus would be a suitable tool to perform more extensive LOH studies. In this European multicentre study, we have examined the occurrence of APOC3 LOH and evaluated the effect of LOH of this chromosomal subregion on the clinical behaviour of the disease in a cohort of 766 breast cancer patients in more detail. LOH for APOC3 was found in 42% of the studied tumours, but it was not found to be significantly associated with any of the studied clinical variables,...

Multilectin Affinity Chromatography for Characterization of Multiple Glycoprotein Biomarker Candidates in Serum from Breast Cancer Patients

“…Clinical findings have supported these observations; for example, studies have demonstrated increased concentrations of apolipoprotein B (25 ) and apolipoprotein C III (26 ) in patients with breast cancer. For the purposes of this study, we selected apolipoprotein C-III as an example of increased serum lipid transport proteins in disease samples; however, other apolipoproteins, such as Lp(a), gave similar results.…”

Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers

“…In addition to the PPP2R1B gene, there may be another gene or genes involved in the development of colorectal cancers at 11q23. So far, several genes involved in tumorigenesis at 11q23–24 have been reported, such as ATM (ataxia-telangiectasia disorder gene at 11q23.1),16 MLL1 (a gene at 11q23 frequently rearranged in acute leukaemia),17 DDX10 (a putative RNA helicase gene at 11q23.1),18 LOH112CR2A (a potential tumour suppressor gene at 11q23),19 Chk1 (a gene at 11q24 encoding a protein kinase required for the DNA damage checkpoint function),20and APOC3 (apolipoprotein C-3 at 11q23) 21. More recently, Wang and colleagues22 reported a second tumour suppressor gene involved in lung cancers located telomeric to PPP2R1B.…”

Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study

“…The observed raised risks of breast cancer, in particular among younger women, point to importance of the 11q23 and 22q11 regions in breast cancer development. Two common regions of loss of heterozygosity have been identified in the region 11q23 in breast cancer . The region 22q11.2 is known to be susceptible to rearrangements and both breakpoints in t(11;22) carriers have been mapped outside gene coding regions to similar palindromic AT‐rich repeats (PATRRs) .…”