Chromosomal comparative genomic hybridization abnormalities in early- and late-onset human breast cancers: correlation with disease progression and TP53 mutations

Jong, Yiin Jeng; Li, Ling Hui; Tsou, Mei Hua; Chen, Yann Jang; Cheng, Skye Hongiun; Wang-Wuu, Sheng; Tsai, Shih Feng; Chen, Chii Ming; Huang, Andrew T.; Hsu, Ming; Lin, Chi

doi:10.1016/s0165-4608(03)00205-x

Cited by 26 publications

(21 citation statements)

References 42 publications

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“…TP53 mutation is strongly associated with high-grade, hormone receptor-negative, basal-like breast tumors and with increased global genomic instability (38)(39)(40)(41)(42), which is a fitting description of BRCA1-related breast tumors (27,43). Furthermore, proteintruncating TP53 mutations have been found to have a prognostic value similar to TP53 hotspot mutations (44) and they have recently been linked to poor prognosis in breast cancer (44) and squamous head and neck cancer patients (45).…”

Section: Discussionmentioning

confidence: 99%

High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer

Holstege¹,

Joosse²,

et al. 2009

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Approximately half of all hereditary breast cancers are compromised in their DNA repair mechanisms due to loss of BRCA1 or BRCA2 function. Previous research has found a strong correlation between BRCA mutation and TP53 mutation. However, TP53 mutation status is often indirectly assessed by immunohistochemical staining of accumulated p53 protein. We sequenced TP53 exons 2 to 9 in 21 BRCA1-related breast cancers and 37 sporadic breast tumors. Strikingly, all BRCA1-related breast tumors contained TP53 mutations, whereas only half of these tumors stained positive for p53 accumulation. Positive p53 staining correlates with the presence of TP53 hotspot mutations in both BRCA1-related and sporadic breast tumors. However, whereas the majority of sporadic breast tumors that stained negative for p53 accumulation had wild-type TP53, the majority of BRCA1-associated breast tumors that stained negative for p53 accumulation had protein-truncating TP53 mutations (nonsense, frameshift, and splice mutations). Therefore, the strong selection for p53 loss in BRCA1-related tumors is achieved by an increase of protein-truncating TP53 mutations rather than hotspot mutations. Hence, immunohistochemical detection of TP53 mutation could lead to misdiagnosis in approximately half of all BRCA1-related tumors. The presence of deleterious TP53 mutations in most, if not all, BRCA1-related breast cancers suggests that p53 loss of function is essential for BRCA1-associated tumorigenesis. BRCA1-related tumors may therefore be treated not only with drugs that target BRCA1 deficiency [e.g., poly(ADP-ribose) polymerase inhibitors] but also with drugs that selectively target p53-deficient cells. This raises interesting possibilities for combination therapies against BRCA1-deficient breast cancers and BRCA1-like tumors with homologous recombination deficiency.

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Section: Discussionmentioning

confidence: 99%

High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer

Holstege¹,

Joosse²,

et al. 2009

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“…Several models or combinations of models have been proposed: long range effect of transcription factors, chromatin structure modification, and increased concentration of components of the transcriptional machinery due to a particular subnuclear location of chromosomal segments (23). Genomic alterations most likely explain part of the correlation between neighboring genes in breast tumors because, except for chromosome arm 14q, the chromosome arms presenting the highest percentage of correlated genes (8q, 51%; 16p, 47%; 17q, 43%; 8p, 40%; 16q, 35%; 20q, 33%; 1q, 32%) were also known to harbor frequent chromosome imbalance, as shown by karyotypic, comparative genomic hybridization, or loss of heterozygosity studies (24)(25)(26)(27)(28)(29)(30). Two well-characterized amplicons, the FGFR1 amplicon at 8p11-p12 and the ERBB2 amplicon at 17q12, corresponded to regions presenting a high percentage of correlated genes.…”

Section: Discussionmentioning

confidence: 99%

Visualizing Chromosomes as Transcriptome Correlation Maps: Evidence of Chromosomal Domains Containing Co-expressed Genes—A Study of 130 Invasive Ductal Breast Carcinomas

et al. 2005

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Completion of the working draft of the human genome has made it possible to analyze the expression of genes according to their position on the chromosomes. Here, we used a transcriptome data analysis approach involving for each gene the calculation of the correlation between its expression profile and those of its neighbors. We used the U133 Affymetrix transcriptome data set for a series of 130 invasive ductal breast carcinomas to construct chromosomal maps of gene expression correlation (transcriptome correlation map). This highlighted nonrandom clusters of genes along the genome with correlated expression in tumors. Some of the gene clusters identified by this method probably arose because of genetic alterations, as most of the chromosomes with the highest percentage of correlated genes (1q, 8p, 8q, 16p, 16q, 17q, and 20q) were also the most frequent sites of genomic alterations in breast cancer. Our analysis showed that several known breast tumor amplicons (at 8p11-p12, 11q13, and 17q12) are located within clusters of genes with correlated expression. Using hierarchical clustering on samples and a Treeview representation of whole chromosome arms, we observed a higher-order organization of correlated genes, sometimes involving very large chromosomal domains that could extend to a whole chromosome arm. Transcription correlation maps are a new way of visualizing transcriptome data. They will help to identify new genes involved in tumor progression and new mechanisms of gene regulation in tumors. (Cancer Res 2005; 65(4): 1376-83)

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“…Loss of the whole arm of this chromosome was found in 20% of early-onset cases ( ! 35 years old, n = 44) compared to 7.4% of late-onset cases ( 1 63 years old, n = 54) by Jong et al [2004]. Frequent allelic deletions were reported at chromosome 11q23-q24 in approximately 50% of breast cancer tissues from mixed populations [Ferti-Passantonopoulou et al, 1991;di Iasio et al, 1999;Wang et al, 2004] and at 11q23-q25 in 11% of breast cancer tissues from women younger than 35 years [Weber-Mangal et al, 2003].…”

Section: Discussionmentioning

confidence: 93%

“…LOH studies have shown extensive loss at 11q24-q25 in early-onset breast cancer and a significant association with poor prognosis and reduced survival [Gentile et al, 1999[Gentile et al, , 2001aChunder et al, 2004;Climent et al, 2007]. The high frequency of LOH at chromosome 11q24.1-11q25 in early-onset breast cancer and the association of this loss with poor prognosis of breast and ovarian neoplasias suggest that this chromosomal region may harbor putative tumor suppressor gene(s) [Ferti-Passantonopoulou et al, 1991;Gabra et al, 1996;di Iasio et al, 1999;Gentile et al, 1999Gentile et al, , 2001aAgrup et al, 2000;Choi et al, 2003;Weber-Mangal et al, 2003;Chunder et al, 2004;Jong et al, 2004;Climent et al, 2007].…”

mentioning

confidence: 99%

Frequent Loss of the <i>BLID</i> Gene in Early-Onset Breast Cancer

Cavalli¹,

Noone²,

Makambi³

et al. 2011

Cytogenet Genome Res

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The BH3-like motif-containing inducer of cell death (BLID) is an intronless gene localized on 11q24.1. Loss of that region has frequently been reported in early-onset breast cancer and is significantly associated with poor prognosis and reduced survival. Downregulation of BLID is associated with younger age, triple-negative phenotype, and reduced disease-free and overall survival of breast cancer patients. In this study, we investigated allelic loss of BLID in breast tumor specimens from 78 women with invasive breast cancer using 2 dinucleotide polymorphic markers closely linked to the BLID gene (no intragenic marker for BLID is available). Seventy-three cases were informative. Overall, loss of heterozygosity (LOH) at the BLID locus was detected in 32% of the informative cases (23/73). However, in patients 40 years old and younger, LOH was detected in 50% of the cases (9/18). Patients aged 40 years and younger were significantly more likely to experience LOH than those aged 41–55 years (p = 0.04). Specifically, the odds of BLID loss for patients aged 40 years and younger were 3.7 times the odds of loss for patients aged 41–55 years (95% CI, 1.1–13). Our findings suggest a tumor suppressor role of the BLID gene in early-onset breast cancer.

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Chromosomal comparative genomic hybridization abnormalities in early- and late-onset human breast cancers: correlation with disease progression and TP53 mutations

Cited by 26 publications

References 42 publications

High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer

High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer

Visualizing Chromosomes as Transcriptome Correlation Maps: Evidence of Chromosomal Domains Containing Co-expressed Genes—A Study of 130 Invasive Ductal Breast Carcinomas

Frequent Loss of the <i>BLID</i> Gene in Early-Onset Breast Cancer

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