• Journal of Korean Neurosurgical Society
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• 제61권3호
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• pp.319-332
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• 2018

Germline mutations in cancer causing genes result in high risk of developing cancer throughout life. These cancer predisposition syndromes (CPS) are especially prevalent in childhood brain tumors and impact both the patient's and other family members' survival. Knowledge of specific CPS may alter the management of the cancer, offer novel targeted therapies which may improve survival for these patients, and enables early detection of other malignancies. This review focuses on the role of CPS in pediatric high grade gliomas (PHGG), the deadliest group of childhood brain tumors. Genetic aspects and clinical features are depicted, allowing clinicians to identify and diagnose these syndromes. Challenges in the management of PHGG in the context of each CPS and the promise of innovative options of treatment and surveillance guidelines are discussed with the hope of improving outcome for individuals with these devastating syndromes.

• BMB Reports
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• 제43권10호
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• pp.693-697
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• 2010

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome characterized by predisposition to early-onset cancers. HNPCC is caused by heterozygous loss-of-function mutations within the mismatch repair genes MLH1, MSH2, MSH6, PMS1, and PMS2. We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery. Five Lynch syndrome patients carried germline mutations in MLH1 or MSH2. Two of these were identified as known mutations in MLH1: deletion of exon 10 and a point mutation (V384D). The remaining three patients exhibited novel mutations: a duplication (937_942dupGAAGTT) in MLH1; deletion of exons 8, 9, and 10; and a point mutation in MLH1 (F396I) combined with multiple missense mutations in MSH2 (D295G, K808E, Q855P, and I884T). The findings underline the importance of efficient pre-screening of conspicuous cases.

• 대한영상의학회지
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• 제83권1호
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• pp.246-251
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• 2022

Li-Fraumeni 증후군(이하 LFS)은 TP53 종양 억제 유전자의 생식세포 돌연변이로 인한 상염색체 우성 종양 유발 유전 질환이다. LFS 환자에서는 치료 후 치료와 관련된 암이 발생하기 때문에 LFS 환자에서 발생한 유방암의 치료에 있어 방사선 요법을 피해야 한다. 저자들은 LFS 환자에서 발생한 유방 육종의 방사선 및 화학 요법 치료 후 발생한 유방암 증례를 보고한다.

• Molecules and Cells
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• 제38권8호
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• pp.669-676
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• 2015

Genome instability, primarily caused by faulty DNA repair mechanisms, drives tumorigenesis. Therapeutic interventions that exploit deregulated DNA repair in cancer have made considerable progress by targeting tumor-specific alterations of DNA repair factors, which either induces synthetic lethality or augments the efficacy of conventional chemotherapy and radiotherapy. The study of Fanconianemia (FA), a rare inherited blood disorder and cancer predisposition syndrome, has been instrumental in understanding the extent to which DNA repair defects contribute to tumorigenesis. The FA pathway functions to resolve blocked replication forks in response to DNA interstrand cross-links (ICLs), and accumulating knowledge of its activation by the ubiquitin-mediated signaling pathway has provided promising therapeutic opportunities for cancer treatment. Here, we discuss recent advances in our understanding of FA pathway regulation and its potential application for designing tailored therapeutics that take advantage of deregulated DNA ICL repair in cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3767-3771
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• 2015

Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. Materials and Methods: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. Results: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. Conclusions: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

• 대한두경부종양학회지
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• 제39권1호
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• pp.23-26
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• 2023

Basal cell carcinoma (BCC) is the most common skin cancer. Ultraviolet radiation exposure and genetic predisposition are known to be the most important etiological factors. Multiple BCC is often associated with genetic familial conditions such as BCC syndrome, basal cell nevus syndrome. We present a case of 54-year-old female who had multiple BCC that had reoccurred. She was completely cured after receiving radio-chemotherapy for leukemia 16 years ago. She had multiple lesions (scalp, left thigh, right popliteal fossa, and right buttock), and had underwent wide excisions of all lesions. All biopsies revealed BCC. Six years later, she had also multiple lesions; left forehead, frontal vertex scalp, parietal vertex scalp, right occipital scalp, and lower abdomen. We performed wide excision. Histopathological examination revealed BCC. She had no signs of any BCC associated syndrome. We report a rare case of nonsyndromic multiple BCC that reoccurred at the new site.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.619-624
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• 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

• Journal of Genetic Medicine
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• 제18권1호
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• pp.38-43
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• 2021

Purpose: Demand for genetic counseling on cancer predisposition syndrome is increasing. We evaluated the psychological effect on counselees after genetic counseling at a clinic in a single center. Materials and Methods: We surveyed a total of 72 enrolled participants who visited a genetic counseling clinic at the Samsung Medical Center (SMC). The initial survey was conducted before the first genetic counseling session, and the second survey was conducted after the second genetic counseling session. A total of 43 participants completed both the initial and second surveys. Results: The initial survey of 72 participants indicated higher feelings of guilt in the group with religion, higher depression and anxiety in the group with a diagnosis of self, and higher anxiety in the group on self-referral to the genetic counseling clinic. In the completed survey of 43 participants, overall decreased depression was observed after the second genetic counseling session (P=0.013). Risk perception and anxiety decreased in the group diagnosed with benign variant/variant of uncertain significance (BV/VUS, 25/3) and increased in the group diagnosed with pathogenic variant (PV, 15). Risk perception and anxiety differed between the BV/VUS and PV groups (P<0.001 and P=0.03, respectively). Conclusion: The genetic counseling clinic at the SMC was effective in ameliorating the depression score. Assessment of survey results revealed different depression scores, feelings of guilt and anxiety, and different effects of the genetic counseling clinic, depending on the subgroups. Understanding the needs and psychological characteristics of different groups is necessary for improving genetic counseling services.