The Experts below are selected from a list of 609 Experts worldwide ranked by ideXlab platform
Maria Luisa Martinezfrias - One of the best experts on this subject based on the ideXlab platform.
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the new wolf hirschhorn syndrome critical region whscr 2 a description of a second case
2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
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the new wolf hirschhorn syndrome critical region whscr 2 a description of a second case
2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf–Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.
Marcella Zollino - One of the best experts on this subject based on the ideXlab platform.
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the new wolf hirschhorn syndrome critical region whscr 2 a description of a second case
2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
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the new wolf hirschhorn syndrome critical region whscr 2 a description of a second case
2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf–Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.
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mapping the wolf hirschhorn syndrome phenotype outside the currently accepted whs critical region and defining a new critical region whscr 2
2003Co-Authors: Marcella Zollino, Marina Murdolo, Rosetta Lecce, Rita Fischetto, Francesca Faravelli, Angelo Selicorni, Cinzia Butte, Luigi Memo, Giuseppe Capovilla, Giovanni NeriAbstract:In an attempt to define the distinctive Wolf-Hirschhorn syndrome (WHS) phenotype, and to map its specific clinical manifestations, a total of eight patients carrying a 4p16.3 microdeletion were analyzed for their clinical phenotype and their respective genotypes. The extent of each individual deletion was established by fluorescence in situ hybridization, with a cosmid contig spanning the genomic region from MSX1 (distal half of 4p16.1) to the subtelomeric locus D4S3359. The deletions were 1.9–3.5 Mb, and all were terminal. All the patients presented with a mild phenotype, in which major malformations were usually absent. It is worth noting that head circumference was normal for height in two patients (those with the smallest deletions [1.9 and 2.2 Mb]). The currently accepted WHS critical region (WHSCR) was fully preserved in the patient with the 1.9-Mb deletion, in spite of a typical WHS phenotype. The deletion in this patient spanned the chromosome region from D4S3327 (190 b4 cosmid clone included) to the telomere. From a clinical point of view, the distinctive WHS phenotype is defined by the presence of typical facial appearance, mental retardation, growth delay, congenital hypotonia, and seizures. These signs represent the minimal diagnostic criteria for WHS. This basic phenotype maps distal to the currently accepted WHSCR. Here, we propose a new critical region for WHS, and we refer to this region as “WHSCR-2.” It falls within a 300–600-kb interval in 4p16.3, between the loci D4S3327 and D4S98-D4S168. Among the candidate genes already described for WHS, LETM1 (leucine zipper/EF-hand-containing transmembrane) is likely to be pathogenetically involved in seizures. On the basis of genotype-phenotype correlation analysis, dividing the WHS phenotype into two distinct clinical entities, a “classical” and a “mild” form, is recommended for the purpose of proper genetic counseling.
Yasufumi Kaneda - One of the best experts on this subject based on the ideXlab platform.
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histone h3 lysine 36 methyltransferase WHSC1 promotes the association of runx2 and p300 in the activation of bone related genes
2014Co-Authors: Yu Fei Lee, Keisuke Nimura, Kotaro Saga, Yasufumi KanedaAbstract:The orchestration of histone modifiers is required to establish the epigenomic status that regulates gene expression during development. WHSC1 (Wolf-Hirschhorn Syndrome candidate 1), a histone H3 lysine 36 (H3K36) trimethyltransferase, is one of the major genes associated with Wolf-Hirshhorn syndrome, which is characterized by skeletal abnormalities. However, the role of WHSC1 in skeletal development remains unclear. Here, we show that WHSC1 regulates gene expression through Runt-related transcription factor (Runx) 2, a transcription factor central to bone development, and p300, a histone acetyltransferase, to promote bone differentiation. WHSC1-/- embryos exhibited defects in ossification in the occipital bone and sternum. WHSC1 knockdown in pre-osteoblast cells perturbed histone modification patterns in bone-related genes and led to defects in bone differentiation. WHSC1 increased the association of p300 with Runx2, activating the bone-related genes Osteopontin (Opn) and Collagen type Ia (Col1a1), and WHSC1 suppressed the overactivation of these genes via H3K36 trimethylation. Our results suggest that WHSC1 fine-tunes the expression of bone-related genes by acting as a modulator in balancing H3K36 trimethylation and histone acetylation. Our results provide novel insight into the mechanisms by which this histone methyltransferase regulates gene expression.
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a histone h3 lysine 36 trimethyltransferase links nkx2 5 to wolf hirschhorn syndrome
2009Co-Authors: Keisuke Nimura, Kiyoe Ura, Hidetaka Shiratori, Masato Ikawa, Masaru Okabe, Robe J Schwartz, Yasufumi KanedaAbstract:Diverse histone modifications are catalysed and recognized by various specific proteins, establishing unique modification patterns that act as transcription signals. In particular, histone H3 trimethylation at lysine 36 (H3K36me3) is associated with actively transcribed regions and has been proposed to provide landmarks for continuing transcription; however, the control mechanisms and functions of H3K36me3 in higher eukaryotes are unknown. Here we show that the H3K36me3-specific histone methyltransferase (HMTase) Wolf-Hirschhorn syndrome candidate 1 (WHSC1, also known as NSD2 or MMSET) functions in transcriptional regulation together with developmental transcription factors whose defects overlap with the human disease Wolf-Hirschhorn syndrome (WHS). We found that mouse WHSC1, one of five putative Set2 homologues, governed H3K36me3 along euchromatin by associating with the cell-type-specific transcription factors Sall1, Sall4 and Nanog in embryonic stem cells, and Nkx2-5 in embryonic hearts, regulating the expression of their target genes. WHSC1-deficient mice showed growth retardation and various WHS-like midline defects, including congenital cardiovascular anomalies. The effects of WHSC1 haploinsufficiency were increased in Nkx2-5 heterozygous mutant hearts, indicating their functional link. We propose that WHSC1 functions together with developmental transcription factors to prevent the inappropriate transcription that can lead to various pathophysiologies.
Marina Murdolo - One of the best experts on this subject based on the ideXlab platform.
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the new wolf hirschhorn syndrome critical region whscr 2 a description of a second case
2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
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the new wolf hirschhorn syndrome critical region whscr 2 a description of a second case
2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf–Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.
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mapping the wolf hirschhorn syndrome phenotype outside the currently accepted whs critical region and defining a new critical region whscr 2
2003Co-Authors: Marcella Zollino, Marina Murdolo, Rosetta Lecce, Rita Fischetto, Francesca Faravelli, Angelo Selicorni, Cinzia Butte, Luigi Memo, Giuseppe Capovilla, Giovanni NeriAbstract:In an attempt to define the distinctive Wolf-Hirschhorn syndrome (WHS) phenotype, and to map its specific clinical manifestations, a total of eight patients carrying a 4p16.3 microdeletion were analyzed for their clinical phenotype and their respective genotypes. The extent of each individual deletion was established by fluorescence in situ hybridization, with a cosmid contig spanning the genomic region from MSX1 (distal half of 4p16.1) to the subtelomeric locus D4S3359. The deletions were 1.9–3.5 Mb, and all were terminal. All the patients presented with a mild phenotype, in which major malformations were usually absent. It is worth noting that head circumference was normal for height in two patients (those with the smallest deletions [1.9 and 2.2 Mb]). The currently accepted WHS critical region (WHSCR) was fully preserved in the patient with the 1.9-Mb deletion, in spite of a typical WHS phenotype. The deletion in this patient spanned the chromosome region from D4S3327 (190 b4 cosmid clone included) to the telomere. From a clinical point of view, the distinctive WHS phenotype is defined by the presence of typical facial appearance, mental retardation, growth delay, congenital hypotonia, and seizures. These signs represent the minimal diagnostic criteria for WHS. This basic phenotype maps distal to the currently accepted WHSCR. Here, we propose a new critical region for WHS, and we refer to this region as “WHSCR-2.” It falls within a 300–600-kb interval in 4p16.3, between the loci D4S3327 and D4S98-D4S168. Among the candidate genes already described for WHS, LETM1 (leucine zipper/EF-hand-containing transmembrane) is likely to be pathogenetically involved in seizures. On the basis of genotype-phenotype correlation analysis, dividing the WHS phenotype into two distinct clinical entities, a “classical” and a “mild” form, is recommended for the purpose of proper genetic counseling.
Ryuji Hamamoto - One of the best experts on this subject based on the ideXlab platform.
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the histone methyltransferase WHSC1 is regulated by ezh2 and is important for ovarian clear cell carcinoma cell proliferation
2019Co-Authors: Machiko Kojima, Ryuji Hamamoto, Kenbun Sone, Katsutoshi Oda, Syuzo Kaneko, Shinya Oki, Asako Kukita, Hidenori Machino, Harunori Honjoh, Yoshiko KawataAbstract:Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1), a histone methyltransferase, has been found to be upregulated and its expression to be correlated with expression of enhancer of zeste homolog 2 (EZH2) in several cancers. In this study, we evaluated the role of WHSC1 and its therapeutic significance in ovarian clear cell carcinoma (OCCC). First, we analyzed WHSC1 expression by quantitative PCR and immunohistochemistry using 23 clinical OCCC specimens. Second, the involvement of WHSC1 in OCCC cell proliferation was evaluated by MTT assays after siRNA-mediated WHSC1 knockdown. We also performed flow cytometry (FACS) to address the effect of WHSC1 on cell cycle. To examine the functional relationship between EZH2 and WHSC1, we knocked down EZH2 using siRNAs and checked the expression levels of WHSC1 and its histone mark H3K36m2 in OCCC cell lines. Finally, we checked WHSC1 expression after treatment with the selective inhibitor, GSK126. Both quantitative PCR and immunohistochemical analysis revealed that WHSC1 was significantly overexpressed in OCCC tissues compared with that in normal ovarian tissues. MTT assay revealed that knockdown of WHSC1 suppressed cell proliferation, and H3K36me2 levels were found to be decreased in immunoblotting. FACS revealed that WHSC1 knockdown affected the cell cycle. We also confirmed that WHSC1 expression was suppressed by EZH2 knockdown or inhibition, indicating that EZH2 is upstream of WHSC1 in OCCC cells. WHSC1 overexpression induced cell growth and its expression is, at least in part, regulated by EZH2. Further functional analysis will reveal whether WHSC1 is a promising therapeutic target for OCCC.
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Additional file 2: of The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation
2019Co-Authors: Machiko Kojima, Ryuji Hamamoto, Kenbun Sone, Katsutoshi Oda, Syuzo Kaneko, Shinya Oki, Asako Kukita, Hidenori Machino, Harunori Honjoh, Yoshiko KawataAbstract:Figure S1. Knockdown of WHSC1 did not suppress cell growth in non-ARID1A mutated OCCC cells. (A) Knockdown of WHSC1 decreased WHSC1 levles as shown by immunoblotting. Then, immunoblotting was performed for WHSC1 and β-actin. (B) Analysis of cell viability after knockdown of WHSC1 for 72 h in RMG1 showed that WHSC1 knockdown did not suppress cell growth. (TIF 81 kb
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Additional file 3: of The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation
2019Co-Authors: Machiko Kojima, Ryuji Hamamoto, Kenbun Sone, Katsutoshi Oda, Syuzo Kaneko, Shinya Oki, Asako Kukita, Hidenori Machino, Harunori Honjoh, Yoshiko KawataAbstract:Figure S2. Knockdown of WHSC1 did not affect the expression of H3K27me3. After OVOTKO cells were transfected with siRNAs (siNC and siWHSC1#1/#2), western blotting was performed. Knockdown of WHSC1 did not affect the expression of H3K27me3. (TIF 85 kb
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abstract 5153 wolf hirschhorn syndrome candidate 1 as a potential novel therapeutic target for head and neck cancer
2014Co-Authors: Vassiliki Saloura, Yusuke Nakamura, Houda Alachkar, Makoto Nakakido, Tanguy Y. Seiwert, Mark W. Lingen, Ezra E W Cohen, Ryuji HamamotoAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Protein lysine methyltransferases (PKMTs) are a class of histone modifiers that have recently been reported to be mutated, amplified and overexpressed in a variety of cancers and are emerging as attractive targets for drug development. Squamous cell carcinoma of the head and neck (SCCHN) is a common malignancy with a poor prognosis. Recently, we found that WHSC1, a protein methyltransferase of the NSD family of PKMTs (NSD1, WHSC1/NSD2, WHSC1L1/NSD3), is overexpressed in 75% of SCCHN patients. In addition, the TCGA project recently reported that the NSD-family of PKMTs is altered in 26% of SCCHN patients in a mutually exclusive pattern. Given the above and the fact that an upcoming WHSC1-inhibitor is under development, we decided to further investigate the role of WHSC1 as a mediator of oncogenesis and thus as a potential novel therapeutic target for SCCHN. Methods: Cytotoxicity assays (MTTs) were performed in one HPV-positive and 3 HPV-negative SCCHN cell lines using WHSC1-specific siRNAs. Annexin V assays were performed to evaluate whether cell death was mediated through apoptosis. Cell cycle analysis by flow cytometry was also performed. Immunohistochemistry for WHSC1 and H3K36me2 was conducted in a cohort of 123 patients with SCCHN. To identify downstream targets of WHSC1, cDNA microarrays were conducted in a loss-of-function SCCHN cell line. ChIP assays were performed to assess transcriptional downstream targets directly regulated by WHSC1. Immunoprecipitation assays and mass spectrometry analysis were conducted and candidate substrates were further characterized by in vitro methyltransferase assay. Results: Knockdown of WHSC1 with WHSC1-specific siRNAs caused significant growth suppression in 4 SCCHN cell lines. Cell death was mediated partially through induction of apoptosis, as evidence by an increase of sub-G1 and annexin V-positive cells. Cell cycle analysis also revealed a significant decrease in the S-phase cells. Survival correlations of WHSC1 in a cohort of 123 SCCHN patients is currently underway. cDNA microarray analysis revealed that knockdown of WHSC1 in a SCCHN cell line was associated with downregulation of genes involved in cellular differentiation, apoptosis and mitosis, including NEK7, MAPK8 and HIPK3, which were validated with qPCR. NEK7 was further validated to be downregulated at the protein level after WHSC1 knockdown. ChIP assay for NEK7 revealed that WHSC1 directly binds to four different gene body regions of NEK7. Conclusions: Based on these data, it is possible that WHSC1 may function as a driver of oncogenesis in SCCHN, and could thus serve as a novel therapeutic target for this disease. With a WHSC1-inhibitor already under development, advancing our knowledge of the function of WHSC1 and the other NSD-PKMTs in SCCHN and other cancer types with NSD-aberrancies could accelerate the introduction of relevant inhibitors in clinical trials. Citation Format: Vassiliki Saloura, Makoto Nakakido, Houda Alachkar, Tanguy Seiwert, Mark Lingen, Ezra Cohen, Yusuke Nakamura, Ryuji Hamamoto. Wolf-Hirschhorn syndrome candidate 1 as a potential novel therapeutic target for head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5153. doi:10.1158/1538-7445.AM2014-5153
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abstract 2979 wolf hirschhorn syndrome candidate 1 plays an important role in the pathogenesis of head and neck cancer
2013Co-Authors: Vassiliki Saloura, Hyun-soo Cho, Ryuji Hamamoto, Mark W. Lingen, Ezra E W Cohen, Can Gong, Seiwert Tanguy, Yusuke NakamuraAbstract:Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone lysine methyltransferase (HMT) which was initially found to be deregulated in a subset of multiple myeloma cells with the t(4;14) (p16;q32) translocation and poor prognosis. Recently, our group as well as others found that WHSC1 was overexpressed in a variety of tumors, including lung and esophageal squamous cell carcinomas, with low or no expression in normal tissues except the testis. Long-term survival of patients with squamous cell carcinoma of the head and neck (SCCHN) remains poor and thus new therapeutic strategies are urgently needed. Epigenetic alterations have mainly been studied as a potential mechanism of progression from dysplasia to squamous cell carcinoma. Given the promising potential of HMTs as novel drug targets and the aforementioned interesting expression patterns, we further investigated the role of WHSC1 in carcinogenesis through immunohistochemical analysis (IHC) using tissue microarrays of 123 locoregionally advanced SCCHN patients, and 6 samples of fibroepithelial hyperplasia lesions obtained from oral biopsies. We classified its expression levels with a scoring scale of 0 (no expression), +1 (mild), +2 (moderate) or +3 (strong). WHSC1 expression in the nucleus and cytoplasm was moderate (score +2, 37%) or strong (score +3, 38%) in 75% of SCCHN samples, while 25% showed mild (score +1, 24%) or no (score 0, 1%) expression. WHSC1 staining of normal epithelial regions revealed an exclusively nuclear expression pattern in the basal and parabasal layers. This is consistent with reports suggesting a physiologic role of the Wnt-pathway, which was recently found to be induced by WHSC1, in the differentiation process of the squamous epithelium. We also performed Western blot analysis of WHSC1 in 8 SCCHN cells lines, 3 control fibroblast cell lines and 1 keratinocyte cell line. We observed moderate to strong overexpression of WHSC1 in 4 of 8 SCCHN cell lines, while no expression was detected in the normal keratinocytes or the fibroblast cell lines. These findings support a potential role of the WHSC1 pathway in the pathogenesis of SCCHN and provides a new therapeutic avenue for drug discovery in this fatal disease. Citation Format: Vassiliki Saloura, Hyun-Soo Cho, Mark Lingen, Terri Li, Can Gong, Seiwert Tanguy, Ezra Cohen, Ryuji Hamamoto, Yusuke Nakamura. Wolf-Hirschhorn syndrome candidate 1 plays an important role in the pathogenesis of head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2979. doi:10.1158/1538-7445.AM2013-2979
