Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer

Gentile, Massimiliano; Wiman, Åsa; Thorstenson, Sten; Loman, Niklas; Borg, Åke; Wingren, Sten

doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1169>3.0.co;2-4

Cited by 19 publications

(16 citation statements)

References 33 publications

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“…In breast cancer, allelic imbalance has been reported to range in magnitude between 30 ± 50% (Hampton et al, 1994;Kerangueven et al, 1997;Koreth et al, 1997;Negrini et al, 1995), a ®gure that was previously con®rmed by our group to be valid also in a population of early onset cases (Gentile et al, 1999b;. We, and others, further found that loss of chromosomal material at several dierent loci in this region confers a more adverse prognosis and a more malignant phenotype (Laake et al, 1999;Gentile et al, 2001). The present study was carried out with the intent to assess the involvement of four candidate genes in breast cancer aecting young women.…”

Section: Discussionsupporting

confidence: 55%

“…Interestingly, our data also showed that LOH of the more telomeric part of this region correlates with higher tumour malignancy grade and reduced survival (Gentile et al, 2001), possibly suggesting that inactivation of a gene at the telomere of 11q might promote a more aggressive tumour phenotype. The present study was carried out in an attempt to identify one or more target genes in this area.…”

Section: Introductionmentioning

confidence: 99%

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Candidate tumour suppressor genes at 11q23–q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis

Gentile¹,

Ahnström²,

Schön³

et al. 2001

Oncogene

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One of the most consistently deleted chromosomal regions in solid tumours is 11q23 ± q25, which consequently has been postulated to harbour one or more tumour suppressor loci. Despite large eorts to identify the responsible genes, the goal remains elusive, but as knowledge accumulates new candidates are emerging. The present study was undertaken in an attempt to assess the possible implication of four genes residing at 11q23 ± q24, in a population of early onset breast cancer (n=41). The coding sequence of PIG8, CHK1, LOH11CR2A and PPP2R1B were screened for mutations using the protein truncation test or single-strand conformational polymorphism, in combination with direct DNA sequencing. Varying proportions of alterations were detected, ranging from 6% in PPP2R1B to 39% in PIG8. Many of these changes were deletions, in some cases corresponding to complete exons, thus likely to represent splice variants, while others were presumed to arise from aberrant splicing, since they occurred at sites with resemblance to exon/intron borders. Considering only bona ®de mutations, the highest alteration frequency (17%) was again found in PIG8. Most of these alterations were likely to have an adverse impact on the translated protein as they either altered the reading frame or aected phylogenetically conserved residues. Our data represent the ®rst evidence of alterations in the PIG8 gene in human malignancies, a ®nding that substantiates its role as a potential tumour suppressor gene as suggested by its involvement in p53-induced apoptosis. Oncogene (2001) 20, 7753 ± 7760.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Candidate tumour suppressor genes at 11q23–q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis

Gentile¹,

Ahnström²,

Schön³

et al. 2001

Oncogene

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“…Genetic analysis of 41 early-onset breast cancers showed that EI24/PIG8 has the highest mutation rate of four candidate tumor suppressor genes located in this area, with many of the mutations predicted to result in frameshifts or complete loss of translation (13). Moreover, this region expresses frequent loss of heterozygosity, suggesting that EI24/PIG8 is perhaps the most important tumor suppressor gene at this locus (14).…”

Section: Introductionsupporting

confidence: 67%

Apoptosis Factor EI24/PIG8 Is a Novel Endoplasmic Reticulum–Localized Bcl-2–Binding Protein which Is Associated with Suppression of Breast Cancer Invasiveness

Zhao¹,

Ayer²,

Davis³

et al. 2005

Cancer Research

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“…amplifications are heterogeneous, a recurrent feature is deletions at the distal part of 11q, which in turn has been connected to adverse prognosis and a malignant phenotype (Launonen et al, 1998;Laake et al, 1999;Gentile et al, 2001). Studies in squamous cell carcinoma cell lines have suggested that 11q13 amplifications are formed through breakage-fusion-bridge cycles, involving an initiating step where distal 11q is lost (Shuster et al, 2000), which may explain the strong coexistence of 11q13 amplifications and loss of distal 11q in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

High‐resolution genomic analysis of the 11q13 amplicon in breast cancers identifies synergy with 8p12 amplification, involving the mTOR targets S6K2 and 4EBP1

Karlsson

Waltersson

Bostner

et al. 2011

Genes Chromosomes & Cancer

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The chromosomal region 11q13 is amplified in 15-20% of breast cancers; an event associated with oestrogen receptor (ER) expression but also implicated in resistance to endocrine therapy. Coamplifications of the 11q13 and 8p12 regions are common, suggesting synergy between the amplicons. The aim was to identify candidate oncogenes in the 11q13 region based on recurrent amplification patterns and correlations to mRNA expression levels.Furthermore, the 11q13/8p12 coamplification and its prognostic value, was evaluated at the DNA and the mRNA levels. Affymetrix 250K NspI arrays were used for whole genome screening of DNA copy number changes in 29 breast tumours. To identify amplicon cores at 11q13 and 8p12, Genomic Identification of Significant Targets in Cancer (GISTIC) was applied. The mRNA expression levels of candidate oncogenes in the amplicons (RAD9A, RPS6KB2 (S6K2), CCND1, FGF19, FGF4, FGF3, PAK1, GAB2 (11q13); EIF4EBP1(4EBP1), PPAPDC1B and FGFR1 (8p12)) were evaluated using real-time PCR. Resulting data revealed three main amplification cores at 11q13. ER expression was associated with the central 11q13 amplification core, encompassing CCND1, whereas 8p12 amplification/gene expression correlated to S6K2 in a proximal 11q13 core. Amplification of 8p12 and high expression of 4EBP1 or FGFR1 was associated with a poor outcome in the group. In conclusion, SNP arrays have enabled mapping of the 11q13 amplicon in breast tumours with high resolution. A proximal 11q13 core including S6K2 was identified as involved in the coamplification/coexpression with 8p12, suggesting synergy between the mTOR targets S6K2 and 4EBP1 in breast cancer development and progression.3

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Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer

Cited by 19 publications

References 33 publications

Candidate tumour suppressor genes at 11q23–q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis

Candidate tumour suppressor genes at 11q23–q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis

Apoptosis Factor EI24/PIG8 Is a Novel Endoplasmic Reticulum–Localized Bcl-2–Binding Protein which Is Associated with Suppression of Breast Cancer Invasiveness

High‐resolution genomic analysis of the 11q13 amplicon in breast cancers identifies synergy with 8p12 amplification, involving the mTOR targets S6K2 and 4EBP1

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