• 제목/요약/키워드: germline mutation

검색결과 31건 처리시간 0.022초

Parental Age-Related Risk of Retinoblastoma in Iranian Children

  • Saremi, Leila;Imani, Saber;Rostaminia, Maryam;Nadeali, Zakiye
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권6호
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    • pp.2847-2850
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    • 2014
  • Background: Retinoblastoma is a rare malignant intraocular neoplasm. About 90% of cases feature a germline mutation in the RB1 gene and these will develop retinoblastoma during their early childhood. An association between mutations in germline cells and aging has been demonstrated. This suggests a higher incidence of childhood cancer including retinoblastoma among children of older parents. Materials and Methods: In the present study we aimed to determine the association of paternal and maternal age with an increased risk of retinoblastoma in a case-control study in Iranian population. The study was carried out on 240 persons who were born during 1984-2012 in Mahak and Mofid hospitals in Tehran, Iran. The statistical analysis included studying the mean age of parents and in order to know whether parental age of patients is different from parental age of control group, (t-test) compare averages test is used perfectly. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The results of statistical analysis including the study of mean parental age by the use of (t-test) compare averages test showed a significant difference between parental ages of patients and controls. Logistic regression showed that coefficients were significant for maternal but not paternal age. Conclusions: Our findings indicate that advanced maternal age can increase the risk of retinoblastoma in offspring, but the paternal age has no significant effect.

Novel Mutations in Cholangiocarcinoma with Low Frequencies Revealed by Whole Mitochondrial Genome Sequencing

  • Muisuk, Kanha;Silsirivanit, Atit;Imtawil, Kanokwan;Bunthot, Suphawadee;Pukhem, Ake;Pairojkul, Chawalit;Wongkham, Sopit;Wongkham, Chaisiri
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권5호
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    • pp.1737-1742
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    • 2015
  • Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

A Pilot Study on Screening of BRCA1 Mutations (185delAG, 1294del40) in Nepalese Breast Cancer Patients

  • Bhatta, Bibek;Thapa, Roshina;Shahi, Sanjay;Bhatta, Yogesh;Pandeya, Dipendra Raj;Poudel, Bal Hari
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1829-1832
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    • 2016
  • Background: Breast cancer is the second most common malignancy among Nepalese women, accounting for 60% of the total cancer cases in females. Women diagnosed with germline mutations in BRCA1 like 185delAG, 1294del40 develop breast and/or ovarian cancer with a lifelong likelihood of up to 85% whereas presence of a mutation increases the risk for mutations to occur in other genes. The major objective of this study was to find the prevalence of these mutations in Nepalese cancer patients. Materials and Methods: This prospective study was carried out at two cancer hospitals in the Kathmandu valley over a period of 11 months. Irrespective of age group and stage of canceran appropriate amount of blood was withdrawn from 50 breast cancer patients and 20 controls. DNA was extracted manually and subjected to PCR using primers for 185delAG and 1294del40 mutations. PCR products were then digested with restriction enzyme (DdeII) followed by electrophoresis. Results: Prevalence of 185delAG in reference breast cancer patients was found to be 4/50 (8%) but no 1294del40 was apparent. Conclusions: Several mutations occurring in different exons of BRCA1 as well as mutations in other genes like BRCA2, for example, should also be taken in account.

Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases

  • Anwar, Sumadi Lukman;Haryono, Samuel J;Aryandono, Teguh;Datasena, I Gusti Bagus
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1987-1991
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    • 2016
  • Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

  • Hansa, Jagadish;Kannan, Ravi;Ghosh, Sankar Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권11호
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    • pp.5871-5874
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    • 2012
  • Around 1.35 million people of worldwide suffer from breast cancer each year, whereas in India, 1 in every 17 women develops the disease. Mutations of the Breast Cancer 1 (BRCA1) gene account for the majority of breast/ovarian cancer families. The purpose of study was to provide a prevalence of BRCA1 germline mutations in the North-East Indian population. In relation to the personal and family history with the breast cancer, we found mutations in 6.25% and 12.5% respectively. Three mutations, 185DelAG, 1014DelGT and 3889DelAG, were observed in our North-East Indian patients in exons 2 and 11, resulting in truncation of the BRCA1 protein by forming stop codons individually at amino acid positions 39, 303 and 1265. Our results point to a necessity for an extensive mutation screening study of high risk breast cancer cases in our North-East Indian population, which will provide better decisive medical and surgical preventive options.

Impressive effect of cisplatin monotherapy on a patient with heavily pretreated triple-negative breast cancer with poor performance

  • Baek, Dong Won;Park, Ji-Young;Lee, Soo Jung;Chae, Yee Soo
    • Journal of Yeungnam Medical Science
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    • 제37권3호
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    • pp.230-235
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    • 2020
  • Systemic therapy for metastatic triple-negative breast cancer (TNBC) still remains challenging because there are no targeted agents or endocrine therapies currently available. The present case report documents the successful use of cisplatin monotherapy to manage a heavily pretreated TNBC patient showing poor response to therapy. The patient was a 51-year-old woman who had already undergone several lines of systemic chemotherapy for widespread TNBC. Although the mutation analysis performed on DNA isolated from blood cells and progressed lesion samples confirmed the tumor to be germline BRCA wild-type, cisplatin monotherapy was administered based on the increasing evidence of safety and efficacy of platinum for breast cancer. After three cycles of cisplatin treatment, the patient's metastatic lesions dramatically improved without any major toxicity, and she completed 17 cycles with good response. This case study indicates that patients with heavily pretreated TNBC can potentially achieve a good response to cisplatin monotherapy.

골육종과 폐선암을 동반한 리-프라우메니 증후군: 증례 보고 (Osteosarcoma with Adenocarcinoma of Lung in Li-Fraumeni Syndrome: A Case Report)

  • 오창선;이진호;정성택;나보람
    • 대한골관절종양학회지
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    • 제20권2호
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    • pp.99-103
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    • 2014
  • Li-Fraumeni syndrome은 소아나 청장년층에서 다양한 형태의 종양을 유발할 수 있는 상염색체 우성 유전 질병이다. 이는 종양억제 유전자인 TP53 의 변형에 의해 발생하게 된다. 이 질환은 매우 드물며, 진단되지 못하고 간과되는 경향이 많다. 이에 저자들은 17세, 폐선암을 동반한 근위 경골 골육종 환자에서 가족력을 통해 이 질환을 의심하고, 유전자 검사를 통하여 확진한 증례를 보고하고자 한다.

Mechanistic Target of Rapamycin Pathway in Epileptic Disorders

  • Kim, Jang Keun;Lee, Jeong Ho
    • Journal of Korean Neurosurgical Society
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    • 제62권3호
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    • pp.272-287
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    • 2019
  • The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

Germline Variations of Apurinic/Apyrimidinic Endonuclease 1 (APEX1) Detected in Female Breast Cancer Patients

  • Ali, Kashif;Mahjabeen, Ishrat;Sabir, Maimoona;Baig, Ruqia Mehmood;Zafeer, Maryam;Faheem, Muhammad;Kayani, Mahmood Akhtar
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권18호
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    • pp.7589-7595
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    • 2014
  • Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein which plays a central role in the BER pathway. APEX1 gene being highly polymorphic in cancer patients and has been indicated to have a contributive role in Apurinic/apyrimidinic (AP) site accumulation in DNA and consequently an increased risk of cancer development. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 530 breast cancer patients and 395 matched healthy controls and then analyzed by single-stranded conformational polymorphism followed by sequencing. Sequence analysis revealed fourteen heterozygous mutations, seven 5'UTR, one 3'UTR, two intronic and four missense. Among identified mutations one 5'UTR (rs41561214), one 3'UTR (rs17112002) and one missense mutation (Ser129Arg, Mahjabeen et al., 2013) had already been reported while the remaining eleven mutations. Six novel mutations (g.20923366T>G, g.20923435G>A, g.20923462G>A, g.20923516G>A, 20923539G>A, g.20923529C>T) were observed in 5'UTR region, two (g.20923585T>G, g.20923589T>G) in intron1 and three missense (Glu101Lys, Ala121Pro, Ser123Trp) in exon 4. Frequencues of 5'UTR mutations; g.20923366T>G, g.20923435G>A and 3'UTR (rs17112002) were calculated as 0.13, 0.1 and 0.1 respectively. Whereas, the frequency of missense mutations Glu101Lys, Ser123Trp and Ser129Arg was calculated as 0.05. A significant association was observed between APEX1 mutations and increased breast cancer by ~9 fold (OR=8.68, 95%CI=2.64 to 28.5) with g.20923435G>A (5'UTR), ~13 fold (OR= 12.6, 95%CI=3.01 to 53.0) with g.20923539G>A (5'UTR) and~5 fold increase with three missense mutations [Glu101Lys (OR=4.82, 95%CI=1.97 to 11.80), Ser123Trp (OR=4.62, 95%CI=1.7 to 12.19), Ser129Arg (OR=4.86, 95%CI=1.43 to 16.53)]. The incidence of observed mutations was found higher in patients with family history and with early menopause. In conclusion, our study demonstrates a significant association between germ line APEX1 mutations and breast cancer patients in the Pakistani population.

한국의 젊은 여성유방암 환자에서 BRCA 배선유전자 돌연변이는 예후인자인가? (Is the BRCA Germline Mutation a Prognostic Factor in Korean Patients with Early-onset Breast Carcinomas?)

  • 최두호;이민혁
    • Radiation Oncology Journal
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    • 제21권2호
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    • pp.149-157
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    • 2003
  • 목적: 한국인 젊은 여성 유방암 환자에서 유방암 유전자 (BRCA)가 예후인자가 될 수 있는지 알아보기 위하여 본 연구를 시행하였다. 대상 및 방법: 대학병원에서 치료를 받은 환자 중에서 유방암이나 난소암의 가족력과 관계없이 40세 이하의 환자를 선택하였다. 환자의 나이는 18~40세이었고 중앙값은 34.5세이었다. 환자의 말초혈액에서 림프구를 모아 DNA를 추출하였으며 BRCA1과 BRCA2의 모든 염기 중에서 기능과 관계 있는 부위의 DNA를 직접염기서열 결정방식으로 검사하였다. 조직표본 검사가 가능한 환자는 면역화학조직검사를 시행하였다. 대상 및 방법: 60명의 환자 중에서 유방암 발생과 직접 관계가 있는 돌연변이가 11개(18.3%) 있었고(BRCA1 6명, BRCA2 5명), 의미를 알기가 곤란한 돌연변이가 7개 있었으며 반 수 이상의 돌연변이는 이제까지 보고되지 않은 것이었다. 그리고 대부분의 돌연변이 환자는 유방암이나 난소암의 가족력이 관찰되지 않았다. 유방암 유전자 돌연변이 환자는 한 명도 치료의 실패가 없었으며 한 면에서 반대측 유방암이 발생하였다. 7년 무병 생존율은 돌연변이 환자에서 50%, 돌연변이와 관계가 없는 환자에서 79%이었고 차이는 없었다. BRCA 관련 종양에서 에스트로젠, 프로제스테론 수용체 음성의 비율이 높았으며 조직학적 분화도가 낮았으나 예후는 비교대상에 비해 나쁘지 않았다. 결론: 한국의 젊은 여성 유방암 환자는 예후가 인자가 있어도 재발률이 낮았으며 유전자 돌연변이 이환율이 높았으나 암의 발현율은 상대적으로 낮은 것으로 추정되었다 이 결과를 확인하기 위해 더 많은 환자 집단과 오랜 추적기간의 연구가 필요하다.