Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas

Oliveira, Marcia Maria Costa de; Oliveira, Sarah Franco Vieira de; Lima, Rubens Silveira de; Urban, Cı́cero de Andrade; Cavalli, Luciane R.; Ribeiro, Enilze Maria de Souza Fonseca; Cavalli, Iglenir João

doi:10.1016/j.humpath.2011.12.008

Cited by 5 publications

(6 citation statements)

References 32 publications

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“…Region 3p22.1 to p11.2 has been reported to be a loss in a number of studies, including [32,68,69,70]. Additionally, we found a gain in 3p26.3 to p23.…”

Section: Resultssupporting

confidence: 70%

Identification of Copy Number Aberrations in Breast Cancer Subtypes Using Persistence Topology

et al. 2015

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DNA copy number aberrations (CNAs) are of biological and medical interest because they help identify regulatory mechanisms underlying tumor initiation and evolution. Identification of tumor-driving CNAs (driver CNAs) however remains a challenging task, because they are frequently hidden by CNAs that are the product of random events that take place during tumor evolution. Experimental detection of CNAs is commonly accomplished through array comparative genomic hybridization (aCGH) assays followed by supervised and/or unsupervised statistical methods that combine the segmented profiles of all patients to identify driver CNAs. Here, we extend a previously-presented supervised algorithm for the identification of CNAs that is based on a topological representation of the data. Our method associates a two-dimensional (2D) point cloud with each aCGH profile and generates a sequence of simplicial complexes, mathematical objects that generalize the concept of a graph. This representation of the data permits segmenting the data at different resolutions and identifying CNAs by interrogating the topological properties of these simplicial complexes. We tested our approach on a published dataset with the goal of identifying specific breast cancer CNAs associated with specific molecular subtypes. Identification of CNAs associated with each subtype was performed by analyzing each subtype separately from the others and by taking the rest of the subtypes as the control. Our results found a new amplification in 11q at the location of the progesterone receptor in the Luminal A subtype. Aberrations in the Luminal B subtype were found only upon removal of the basal-like subtype from the control set. Under those conditions, all regions found in the original publication, except for 17q, were confirmed; all aberrations, except those in chromosome arms 8q and 12q were confirmed in the basal-like subtype. These two chromosome arms, however, were detected only upon removal of three patients with exceedingly large copy number values. More importantly, we detected 10 and 21 additional regions in the Luminal B and basal-like subtypes, respectively. Most of the additional regions were either validated on an independent dataset and/or using GISTIC. Furthermore, we found three new CNAs in the basal-like subtype: a combination of gains and losses in 1p, a gain in 2p and a loss in 14q. Based on these results, we suggest that topological approaches that incorporate multiresolution analyses and that interrogate topological properties of the data can help in the identification of copy number changes in cancer.

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“…Region 3p22.1 to p11.2 has been reported to be a loss in a number of studies, including [32,68,69,70]. Additionally, we found a gain in 3p26.3 to p23.…”

Section: Resultssupporting

confidence: 70%

Identification of Copy Number Aberrations in Breast Cancer Subtypes Using Persistence Topology

et al. 2015

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“…In our study, the frequency of LOH at the FHIT gene detected by the intragenic marker D3S1300 was 31.1% (52 out of 167 informative cases). According to previous published data, FHIT LOH frequencies range from 24% to 45%, considering different BC's populations [8][9]11,[18][19][20] .…”

Section: Discussionmentioning

confidence: 99%

“…Ahmadian et al [7] inferred that FHIT LOH would be an early but not independent event in BC's carcinogenesis. De Oliveira et al [8] have shown an association between FHIT LOH and ductal BC subtype. While Santos et al [9] ÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿ found no connections between BC's clinical features and FHIT LOH.…”

Section: Introductionmentioning

confidence: 99%

The Loss of Heterozygosity of FHIT Gene in Sporadic Breast Cancer

Zavalhia

Damin

Agnes

et al. 2021

Jour. of oncol. res.

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The loss of heterozygosity (LOH) is a genetic event that can change gene function. FHIT is a potential tumor suppressor gene. Although the precise FHIT molecular mechanism of action is not well understood, evidences suggest that Fhit protein reduced levels are involved in mammary carcinogenesis. The aim of this study was to investigate if FHIT LOH could influence on sporadic breast cancer (BC) biological behavior, through its association with prognostic factors for sporadic BC.Tumor tissue and peripheral blood samples were analyzed using the microsatellite marker D3S1300. The findings were associated with clinicopathological parameters including overall survival. LOH was detected in 31.1%(52/167) of the informative BC’ cases. Considering clinical and pathological characteristics we have found no significant association with FHIT LOH status. The mean follow-up time was 80 months. After the Cox regression analysis two parameters remained associated with BC’s risk of death: TNM stage III and IV - HR = 3.74(95% CI, 1.16-12.1) P=0.027 and disease relapse HR = 3.14(CI 95% 1.26-7.80) P =0.014. This study shows that FHIT LOH by itself is not a prognostic factor for sporadic BC. Further researches are required to elucidate the functional role of FHIT LOH concerning to BC.

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“…FAM107A, originally identified in a commonly deleted region on 3p21 in renal cell carcinoma, appears to function as a tumour suppressor [ 24 – 26 ]. Loss of heterozygosity at 3p21 is common in human malignancies [ 24 , 27 – 30 ], although the region has not been shown to be recurrently lost or gained in primary HRS cells [ 31 , 32 ]. However, both cHL and non-Hodgkin lymphoma have been reported to display chromosomal rearrangements involving this region by fluorescent in situ hybridization [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Combined linkage and association analysis of classical Hodgkin lymphoma

et al. 2018

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The heritability of classical Hodgkin lymphoma (cHL) has yet to be fully deciphered. We report a family with five members diagnosed with nodular sclerosis cHL. Genetic analysis of the family provided evidence of linkage at chromosomes 2q35-37, 3p14-22 and 21q22, with logarithm of odds score >2. We excluded the possibility of common genetic variation influencing cHL risk at regions of linkage, by analysing GWAS data from 2,201 cHL cases and 12,460 controls. Whole exome sequencing of affected family members identified the shared missense mutations p.(Arg76Gln) in FAM107A and p.(Thr220Ala) in SLC26A6 at 3p21 as being predicted to impact on protein function. FAM107A expression was shown to be low or absent in lymphoblastoid cell lines and SLC26A6 expression lower in lymphoblastoid cell lines derived from p.(Thr220Ala) mutation carriers. Expression of FAM107A and SLC26A6 was low or absent in Hodgkin Reed-Sternberg (HRS) cell lines and in HRS cells in Hodgkin lymphoma tissue. No sequence variants were detected in KLHDC8B, a gene previously suggested as a cause of familial cHL linked to 3p21. Our findings provide evidence for candidate gene susceptibility to familial cHL.

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Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas

Cited by 5 publications

References 32 publications

Identification of Copy Number Aberrations in Breast Cancer Subtypes Using Persistence Topology

Identification of Copy Number Aberrations in Breast Cancer Subtypes Using Persistence Topology

The Loss of Heterozygosity of FHIT Gene in Sporadic Breast Cancer

Combined linkage and association analysis of classical Hodgkin lymphoma

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