• BMB Reports
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• 제44권5호
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• pp.317-322
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• 2011

Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed.

• 대한의생명과학회지
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• 제9권3호
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• pp.171-175
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• 2003

Microsatellite instability (MSI), which is caused by a deficient mismatch repair system, is seen in most of the hereditary non-polyposis colon cancers (HNPCC) and a portion of sporadic colorectal cancers. Forty unselected colorectal cancer patients were analyzed for MSI using silver stain plus kit. The overall incidence of MSI in studied cases was 17％ (7/40). The incidence is similar result with previous study. MSI in colorectal carcers was more prevalent in moderative differentiated adenocarcinoma than well differentiated adenocarcinoma

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4647-4652
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• 2015

Background: Colorectal cancer (CRC) is becoming one of the most complicated challenges of human health, particularly in developing countries like Iran. In this paper, we try to characterize CRC cases diagnosed < age 50 at-risk for Lynch syndrome within central Iran. Materials and Methods: We designed a descriptive retrospective study to screen all registered CRC patients within 2000-2013 in Poursina Hakim Research Center (PHRC), a referral gastroenterology clinic in central Iran, based on being early-onset (age at diagnosis ${\leq}50years$) and Amsterdam II criteria. We calculated frequencies and percentages by SPSS 19 software to describe clinical and family history characteristics of patients with early-onset CRC. Results: Overall 1,659 CRC patients were included in our study of which 413 (24.9%) were ${\leq}50years$ at diagnosis. Of 219/413 successful calls 67 persons (30.6%) were reported deceased. Family history was positive for 72/219 probands (32.9%) and 53 families (24.2%) were identified as familial colorectal cancer (FCC), with a history of at-least three affected members with any type of cancer in the family, of which 85% fulfilled the Amsterdam II Criteria as hereditary non-polyposis colorectal cancer (HNPCC) families (45/219 or 20.5%). Finally, 14 families were excluded due to proband tumor tissues being unavailable or unwillingness for incorporation. The most common HNPCC-associated extracolonic-cancer among both males and females of the families was stomach, at respectively 31.8 and 32.7 percent. The most common tumor locations among the 31 probands were rectum (32.3%), sigmoid (29.0%), and ascending colon (12.9%). Conclusions: Given the high prevalence of FCC (~1/4 of early-onset Iranian CRC patients), it is necessary to establish a comprehensive cancer genetic counseling and systematic screening program for early detection and to improve cancer prognosis among high risk families.

• Journal of Chest Surgery
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• 제33권1호
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• pp.60-67
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• 2000

Background: Microsatellites are short-tandem repeated uncleotide sequences present throughout the human genome. Alterations of microsatellites have been termed microsatellite instability(MI). It has been generally known that microsatellite instability detected in hereditary non-polyposis colorectal cancer (HNPCC) reflects genetic instability that is caused by impairments of DNA mismatch repair system regarding as a novel tumorigenic mechanism. A number of studies reported that MI occurred at varying frequencies in non-small cell lung carcinoma (NSCLC). However It has been unproven whether MI could be a useful market of genetic instability and have a clinical significance in NSCLC. Material and Method : We have examined whether MI can be observed in thirty NCSLC using polymerase chain reaction whether such alterations are associated with other molecular changes such as p53, K-ras and c-myc oncoproteins expression detected by immunohistochemical stain,. Result: MI(+) was observed in 16.6%(5/30) and MI(-) was 83.3% (25/30) Average age was 50$\pm$7.5 year-old in MI(+) group and 57$\pm$6.6 year-old in MI(-) group. Two year survival rate in MI(=) group (20% 1/5) was worse than MI(-) group (64% 16/25) with a statistic difference. (P=0.04) The positive rate of K-ras oncoprotein expression and simultaneous expression of 2 or 3 oncoproteins expression were higher in MI(+) group than MI(-) group with a statistic difference(P=0.05, P=0.01) Conclusion: From, these results the authors can conclude that MI is found in some NSCLC and it may be a novel tumorigenic mechanism in some NSCLC. We also conclude that MI could be used as another poor prognostic factor in NSCLS.

• 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.

• Journal of Genetic Medicine
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• 제7권1호
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• pp.24-36
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• 2010

대장암은 우리나라에서 가장 급격하게 발생이 증가하는 암종의 하나로 유전성 대장암은 전체 대장암의 5-15%를 차지한다. 유전성 대장암은 크게 유전성 비용종증 대장암과 유전성 용종 증후군에서 발생하는 대장암으로 나눌 수 있고, 유전성 용종 증후군에는 가족성 용종증, 포이츠-예거증후군, 유년기 용종증, MYH 연관 용종증 등이 이에 해당한다. 유전성 대장암은 원인 유전자의 배선돌연변이에 기인하므로 산발성 대장암에 비하여 암이 조기 발생하고, 동시성 및 이시성 암이 흔하며, 대장 이외의 장기에도 종양을 비롯한 질병을 일으키는 특징이 있다. 유전성 대장암은 환자뿐 아니라 가족구성원에 대한 유전자 검사, 유전 상담, 조기 진단을 위한 정기검진이 매우 중요하며, 이러한 환자 및 가족구성원의 효율적 관리를 위한 유전성종양 등록소의 역할이 중요하다. 본 논문에서는 유전성 대장암에 해당하는 질환들의 임상적/유전적 특성, 치료, 유전자 검사 및 정기검진 프로그램에 대하여 고찰하고자 한다.