Germline copy number variations associated with breast cancer susceptibility in a Japanese population

Suehiro, Yutaka; Okada, Takae; Shikamoto, Naoya; Zhan, Yibo; Sakai, Kohei; Okayama, Naoko; Nishioka, Michio; Furuya, Tomoko; Oga, Atsunori; Kawauchi, Shigeto; Maeda, Nobuyo; Tamesa, Michiko; Nagashima, Yukiko; Yamamoto, Shigeru; Oka, M.; Hinoda, Yuji; Sasaki, Kohsuke

doi:10.1007/s13277-012-0630-x

Cited by 15 publications

(20 citation statements)

References 27 publications

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“…In an experimental model, the overexpression of PCSK6 in immortalized non-tumorigenic or papilloma-derived keratinocytes increased their invasiveness (24), whereas absent or reduced PCSK6 expression was linked to ovarian cancer (25). Reduced germline copy number of PCSK6 was also reported to be associated with breast cancer risk (16). These reports may support the present data that reduced copy number of germline PCSK6 may confer tumor aggressiveness, thus leading to poor disease progression in NMIBC.…”

Section: Univariate Analysissupporting

confidence: 90%

“…Array image analysis and data normalization were performed with NimbleScan version 2.5 software (Roche Diagnostics). The normalized data were then processed using Nexus Copy Number version 5.0 software (BioDiscovery, Inc., El Segundo, CA, USA) as previously described (16).…”

Section: Methodsmentioning

confidence: 99%

“…Previous reports demonstrated the association between CNVs and the risk of several human malignancies (11)(12)(13)(14)(15)(16). PCSK6 is a member of the protease family of proprotein convertases, which activate precursor proteins by cleaving at the specific recognition sequence RXK/RR (20).…”

Section: Univariate Analysismentioning

confidence: 99%

“…Third, there is a possibility of false positive results in array CGH analysis. CNVs detected by array CGH assay harbor false positives due to a poor signal-to-noise ratio of hybridizations, which leads to considerable variation in the reported CGH ratio (16). Therefore, qPCR with a larger cohort should be carried out to confirm the CNVs that appeared to be associated with bladder cancer susceptibility.…”

Section: Univariate Analysismentioning

confidence: 99%

“…Recent studies have described germline CNVs as potential susceptibility loci for a range of diseases, including infectious, autoimmune and neuropsychiatric diseases (7)(8)(9)(10). Concerning malignancies, CNVs have recently been reported as markers predisposing individuals to neuroblastoma, prostate cancer, pancreatic cancer, colorectal cancer, ovarian cancer and breast cancer risk (11)(12)(13)(14)(15)(16). However, the significance of CNVs in NMIBC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

et al. 2017

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Abstract. Accumulating evidence has suggested that germline DNA copy number variations (CNVs) affect various disorders, including human malignancies. However, the significance of CNVs in non-muscle invasive bladder cancer (NMIBC) remains unclear. The purpose of the present study was to identify the role of CNVs in NMIBC. Array comparative genomic hybridization (CGH) analysis was performed to search for candidate CNVs associated with NMIBC susceptibility. Quantitative polymerase chain reaction was carried out to evaluate CNVs associated with patient outcome in 189 NMIBC cases. In total, 11 CNVs were associated with NMIBC risk in array CGH analysis. Out of the 189 CNVs examined, family with sequence similarity 81 member A (FAM81A) and proprotein convertase subtilisin/kexin type 6 (PCSK6) CNVs exhibited a significant association with recurrence and disease progression in NMIBC. PCSK6 has been reported to regulate proliferation and tumor progression in breast and prostate malignancies. Notably, patients with pT1 stage had significantly lower PCSK6 relative copy number than those with pTa (P=0.0196). In multivariate analyses, PCSK6 copy number was an independent prognostic factor for progression-free survival (P=0.0456; risk ratio, 2.17; 95% confidence interval, 1.02-4.82). These data suggest that PCSK6 CNV is a potential new tumor marker for estimating disease progression in NMIBC.

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Section: Univariate Analysissupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Univariate Analysismentioning

confidence: 99%

Section: Univariate Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

et al. 2017

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Multiplexed Target Detection Using DNA-Binding Dye Chemistry in Droplet Digital PCR

et al. 2013

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Two years ago, we described the first droplet digital PCR (ddPCR) system aimed at empowering all researchers with a tool that removes the substantial uncertainties associated with using the analogue standard, quantitative real-time PCR (qPCR). This system enabled TaqMan hydrolysis probe-based assays for the absolute quantification of nucleic acids. Due to significant advancements in droplet chemistry and buoyed by the multiple benefits associated with dye-based target detection, we have created a "second generation" ddPCR system compatible with both TaqMan-probe and DNA-binding dye detection chemistries. Herein, we describe the operating characteristics of DNA-binding dye based ddPCR and offer a side-by-side comparison to TaqMan probe detection. By partitioning each sample prior to thermal cycling, we demonstrate that it is now possible to use a DNA-binding dye for the quantification of multiple target species from a single reaction. The increased resolution associated with partitioning also made it possible to visualize and account for signals arising from nonspecific amplification products. We expect that the ability to combine the precision of ddPCR with both DNA-binding dye and TaqMan probe detection chemistries will further enable the research community to answer complex and diverse genetic questions.

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A novel somatic mutation of SIN3A detected in breast cancer by whole-exome sequencing enhances cell proliferation through ERα expression

Watanabe

Yamamoto

Sakaguti

et al. 2018

Sci Rep

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Breast cancer is the most frequent tumor in women, and in nearly two-thirds of cases, the tumors express estrogen receptor α (ERα, encoded by ESR1). Here, we performed whole-exome sequencing of 16 breast cancer tissues classified according to ESR1 expression and 12 samples of whole blood, and detected 310 somatic mutations in cancer tissues with high levels of ESR1 expression. Of the somatic mutations validated by a different deep sequencer, a novel nonsense somatic mutation, c.2830 C>T; p.Gln944*, in transcriptional regulator switch-independent 3 family member A (SIN3A) was detected in breast cancer of a patient. Part of the mutant protein localized in the cytoplasm in contrast to the nuclear localization of ERα, and induced a significant increase in ESR1 mRNA. The SIN3A mutation obviously enhanced MCF7 cell proliferation. In tissue sections from the breast cancer patient with the SIN3A c.2830 C>T mutation, cytoplasmic SIN3A localization was detected within the tumor regions where nuclear enlargement was observed. The reduction in SIN3A mRNA correlates with the recurrence of ER-positive breast cancers on Kaplan-Meier plots. These observations reveal that the SIN3A mutation has lost its transcriptional repression function due to its cytoplasmic localization, and that this repression may contribute to the progression of breast cancer.

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Germline copy number variations associated with breast cancer susceptibility in a Japanese population

Cited by 15 publications

References 27 publications

Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

Multiplexed Target Detection Using DNA-Binding Dye Chemistry in Droplet Digital PCR

A novel somatic mutation of SIN3A detected in breast cancer by whole-exome sequencing enhances cell proliferation through ERα expression

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