• Title/Summary/Keyword: Somatic mutation

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Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

  • Cho, Hee Jin;Koo, JaeHyung
    • BMB Reports
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    • v.54 no.12
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    • pp.601-607
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    • 2021
  • Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in > 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma.

Effect of NaCl Treatment and Gamma Ray Irradiation on the Induction Pink Mutations in Hairs of Tradescantia Stamen (NaCl 처리와 감마선조사가 자주달개비 수술털 세포의 분홍돌연변이 유기에 미치는 영향)

  • Kim, Jin-Kyu;Kim, Won-Rok;Kim, Jae-Sung;Kim, Ki-Nam;Hong, Kwang-Phyo
    • Korean Journal of Environmental Agriculture
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    • v.18 no.1
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    • pp.41-47
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    • 1999
  • To investigate the combined effect of gamma ray irradiation and NaCl treatment on Tradescantia somatic cell pink mutations, potted plants of Tradescantia 4430 were evenly sprayed with NaCl solution(170mM) 24 hours before irradiation(NaCl+${\gamma}$) and after irradiation(${\gamma}$+NaCl). Irradiation doses were 0.3, 0.5, 1.0 and 2.0 Gy of gamma-ray. The plants irradiated only with gamma radiation were used as control group(CT). Frequency of pink mutation increased linearly with irradiation close and the peak interval of elevated mutation frequencies appeared during 6∼12 days aver irradiation in all the experimental groups. The slope of dose-response curve in CT was 5.99($r^2$=0.99), while it were 4.55($r^2$=0.98) in NaCl+${\gamma}$ and 4.33($r^2$=0.99) in ${\gamma}$+NaCl. It seemed that pre- and post-treatment of NaCl had a protective effect it against radiation-induced cell damages since it decreased the slope value by more than 24%. It is suggested that protective effect on DNA damages can be invoked in irradiated stamen hair cells by NaCl treatment.

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Protective Effect of Pesticide on Radiation-Induced Cell Damage in Tradescantia 4430 Stamen Hairs (자주달개비 수술털에서 방사선에 의해 유발되는 세포손상에 대한 살충제의 방어효과)

  • 김진규;김원록;이창주;장화형;이영근
    • Korean Journal of Environmental Biology
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    • v.17 no.1
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    • pp.21-26
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    • 1999
  • To investigate the combined effect of radiation and pesticide on Tradescantia somatic cell mutations, potted plants of Tradescantia 4430 on which parathion had been sprayed evenly 24 hours before irradiation. Radiation doses were 0.3, 0.5, 1.0 and 2.0 Gy of gamma-ray. The plants irradiated only with the gamma-ray radiation were used as control groups (CT). Pink mutation frequency increased linearly proportional to the radiation dose and the peak interval of elevated mutation frequencies appeared during 7 ~ 11 days after irradiation in both CT and Pa +${\gamma}$ groups. The slope of dose -response curve in CT was 5.99 ($r^2$= 0.988), while it was 3.43 (r$x^-2$=0.981) in Pa+${\gamma}$. It seemed that parathion pretreatment had a protective effect against radiation-induced cell damages since it decreased the slope value by 43%. It is suggested that an adaptive response or radiomodification could be induced in irradiated stamen hair cells by parathion pretreatment.

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MICROSATELLITE INSTABILITY AND p53 GENE MUTATION IN ORAL SQUAMOUS CELL CARCINOMA (구강편평상피세포암 조직에서의 Microsatellite 불안정성 및 p53 유전자 돌연변이 분석)

  • Choi, Tae-Ho;Chung, Woon-Bok;Hong, Su-Hyung;Kim, Jin-A;Na, Sun-Oung;Jang, Hyun-Jung;Sohn, Yoon-Kyung;Kim, Chin-Soo;Kim, Jung-Wan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.4
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    • pp.337-344
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    • 2000
  • Germ-line mutations at DNA repair loci confer susceptibility to colon cancer in hereditary non-polypopsis colorectal cancer. Somatic loss of DNA mismatch repair gene has been reported in a large variety of other tumor types. Replication errors(RERs) judged by microsatellite instability(MSI) and its associated mutations have been recognized as an important mechanism in various tumor types. To investigate associations between MSI and oral squamous cell carcinoma, the frequency of MSI using 12 microsatellite markers were analyzed for the series of oral tumors. Of 17 tumors, 8 cases(47%) did not show instability at any of the 12 loci; 5(29%) showed instability at $2{\sim}3$ loci; and 4(24%) showed instability above 4 loci. The 4 cases showing widespread MSI did not differ from those without evidence of instability in terms of age at diagnosis, degree of differentiation, metastasis to lymph node, tumor location or the presence of mutations in the p53 tumor suppressor gene. DCC and D17S 796 were the most frequently detected in MSI analysis. There were no correlation between smoking and MSI frequency, instead, smoking was suggested to increase the mutation rate of p53 and development of oral carcinomas.

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Relationship between 18F-FDG PET/CT Semi-Quantitative Parameters and International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society Classification in Lung Adenocarcinomas

  • Lihong Bu;NingTu;Ke Wang;Ying Zhou;Xinli Xie;Xingmin Han;Huiqin Lin;Hongyan Feng
    • Korean Journal of Radiology
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    • v.23 no.1
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    • pp.112-123
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    • 2022
  • Objective: To investigate the relationship between 18F-FDG PET/CT semi-quantitative parameters and the International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histopathologic classification, including histological subtypes, proliferation activity, and somatic mutations. Materials and Methods: This retrospective study included 419 patients (150 males, 269 females; median age, 59.0 years; age range, 23.0-84.0 years) who had undergone surgical removal of stage IA-IIIA lung adenocarcinoma and had preoperative PET/CT data of lung tumors. The maximum standardized uptake values (SUVmax), background-subtracted volume (BSV), and background-subtracted lesion activity (BSL) derived from PET/CT were measured. The IASLC/ATS/ERS subtypes, Ki67 score, and epidermal growth factor/anaplastic lymphoma kinase (EGFR/ALK) mutation status were evaluated. The PET/CT semi-quantitative parameters were compared between the tumor subtypes using the Mann-Whitney U test or the Kruskal-Wallis test. The optimum cutoff values of the PET/CT semi-quantitative parameters for distinguishing the IASLC/ATS/ERS subtypes were calculated using receiver operating characteristic curve analysis. The correlation between the PET/CT semi-quantitative parameters and pathological parameters was analyzed using Spearman's correlation. Statistical significance was set at p < 0.05. Results: SUVmax, BSV, and BSL values were significantly higher in invasive adenocarcinoma (IA) than in minimally IA (MIA), and the values were higher in MIA than in adenocarcinoma in situ (AIS) (all p < 0.05). Remarkably, an SUVmax of 0.90 and a BSL of 3.62 were shown to be the optimal cutoff values for differentiating MIA from AIS, manifesting as pure ground-glass nodules with 100% sensitivity and specificity. Metabolic-volumetric parameters (BSV and BSL) were better potential independent factors than metabolic parameters (SUVmax) in differentiating growth patterns. SUVmax and BSL, rather than BSV, were strongly or moderately correlated with Ki67 in most subtypes, except for the micropapillary and solid predominant groups. PET/CT parameters were not correlated with EGFR/ALK mutation status. Conclusion: As noninvasive surrogates, preoperative PET/CT semi-quantitative parameters could imply IASLC/ATS/ERS subtypes and Ki67 index and thus may contribute to improved management of precise surgery and postoperative adjuvant therapy.

Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone

  • Yoon, Seon-Jin;Park, Junseong;Jang, Dong-Su;Kim, Hyun Jung;Lee, Joo Ho;Jo, Euna;Choi, Ran Joo;Shim, Jin-Kyung;Moon, Ju Hyung;Kim, Eui-Hyun;Chang, Jong Hee;Lee, Jeong Ho;Kang, Seok-Gu
    • Journal of Korean Neurosurgical Society
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    • v.63 no.1
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    • pp.26-33
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    • 2020
  • Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.

Association of Two Polymorphisms of DNA Polymerase Beta in Exon-9 and Exon-11 with Ovarian Carcinoma in India

  • Khanra, Kalyani;Panda, Kakali;Bhattacharya, Chandan;Mitra, A.K.;Sarkar, Ranu;Bhattacharyya, Nandan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1321-1324
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    • 2012
  • Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Conclusion: Hence, the results indicate that there is a tendency for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

The Musculoskeletal Tumors of Werner's Syndrome (워너 증후군에 발생하는 근골격계 종양)

  • Lee, Sang-Hoon;Suh, Sung-Wook;Yoo, Kwang-Hyun;Kim, Han-Soo;Ishikawa, Yuichi;Goto, Makoto
    • The Journal of the Korean bone and joint tumor society
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    • v.8 no.3
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    • pp.69-75
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    • 2002
  • Werner's syndrome is a rare autosomal recessive disorder manifesting as premature aging. It is also known to be characterized by a high frequency of malignant tumors, especially sarcomas. However, Werner's syndrome may be not only a premature aging disease but also a cancer syndrome, because the malignant tumors in these patients are different from those of normal population with respect to involved site, histological type, and age of onset. Recent studies found Werner's syndrome was caused by a mutation of Werner helicase suggesting that WRN helicase may participate in metabolism and repair of DNA. And a dysfunction of WRN helicase may induce the genomic instability causing somatic mutations. Further studies of Werner's syndrome associated with sarcoma might give much informations about the normal aging process and the pathogenesis of sarcomas.

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Concept and limitation of breast cancer stem cells (유방암 줄기세포 개념 및 제한점)

  • Kim, Jong Bin;An, Jeong Shin;Lim, Woosung;Moon, Byung-In
    • Journal of Medicine and Life Science
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    • v.15 no.2
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    • pp.46-50
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    • 2018
  • Cancer, a leading mortality disease following cardiovascular disease worldwide, has high incidence as one out of every four adults in Korea. It was known to be caused by several reasons including somatic mutation, activation of oncogene and chromosome aneuploidy. Cancer cells show a faster growth rate and have metastatic and heterogeneous cell populations compared to normal cells. Cancer stem cells, the most invested field in cancer biology, is a theory to explain heterogeneous cell populations of cancer cells among several characteristics of cancer cells, which is providing the theoretical background for incidence of cancer and treatment failure by drug resistance. Cancer stem cells initially explain heterogeneous cell populations of cancer cells based on the same markers of normal stem cells in cancer, in which only cancer stem cells showed heterogeneity of cancer cells and tumor initiating ability of leukemia. Based on these results, cancer stem cells were reported in various solid cancers such as breast cancer, liver cancer, and lung cancer. Breast cancer stem cells were first reported in solid cancer which had tumor initiating ability and further identified as anti-cancer drug resistance. There were several identification methods in breast cancer stem cells such as specific surface markers and culture methods. The discovery of cancer stem cells not only explains heterogeneity of cancer cells, but it also provides theoretical background for targeting cancer stem cells to complete elimination of cancer cells. Many institutes have been developing new anticancer drugs targeting cancer stem cells, but there have not been noticeable results yet. Many researchers also reported a necessity for improvement of current concepts and methods of research on cancer stem cells. Herein, we discuss the limitations and the perspectives of breast cancer stem cells based on the current concept and history.

Chromosomal Localization and Mutation Detection of the Porcine APM1 Gene Encoding Adiponectin (Adiponectin을 암호화하는 돼지 APM1 유전자의 염색체상 위치파악과 돌연변이 탐색)

  • Park, E.W.;Kim, J.H.;Seo, B.Y.;Jung, K.C.;Yu, S.L.;Cho, I.C.;Lee, J.G.;Oh, S.J.;Jeon, J.T.;Lee, J.H.
    • Journal of Animal Science and Technology
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    • v.46 no.4
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    • pp.537-546
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    • 2004
  • Adiponectin is adipocyte complement-related protein which is highly specialized to play important roles in metabolic and honnonal processes. This protein, called GBP-28, AdipoQ, and Acrp30, is encoded by the adipose most abundant gene transcript 1 (APM1) which locates on human chromosome 3q27 and mouse chromosome 16. In order to determine chromosomal localization of the porcine APM1, we carried out PCR analysis using somatic cell hybrid panel as well as porcine whole genome radiation hybrid (RH) panel. The result showed that the porcine APM1 located on chromosome 13q41 or 13q46-49. These locations were further investigated with the two point analysis of RH panel, revealed the most significant linked marker (LOD score 20.29) being SIAT1 (8 cRs away), where the fat-related QTL located. From the SSCP analysis of APM1 using 8 pig breeds, two distinct SSCP types were detected from K~ native and Korean wild pigs. The determined sequences in Korean native and Korean wild pigs showed that two nucleotide positions (T672C and C705G) were substituted. The primary sequence of the porcine APM1 has 79 to 87% identity with those of human, mouse, and bovine APM1. The domain structures of the porcine APM1 such as signal sequence, hypervariable region, collagenous region. and globular domain are also similar to those of mammalian genes.