Clinical characteristics and mutation analysis of the LKB1 gene in a Peutz-Jeghers syndrome pedigree / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate clinical characteristics and mutation of the LKB1 gene in a Peutz-Jeghers syndrome (PJS) pedigree.</p><p><b>METHOD</b>Clinical data of a PJS family were analyzed and LKB1 gene mutation was detected by systematic screening with multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing. Meanwhile, two hundred and fifty healthy adults were enrolled in this study and denaturing high performance liquid chromatography (PCR-DHPLC) was carried out to verify the mutation excluding polymorphism sites found in this family. Changes in protein structure and function caused by the mutated coding sequence was analyzed by SWISS-MODEL software.</p><p><b>RESULT</b>The proband had pigmented mucocutaneous lesions and multiple hamartomatous polyps in the gastrointestinal tract. There was no fragment deletion of LKB1 gene detected by MLPA. Among PJS family and 250 healthy adults, germline mutation c. 924G > C of LKB1 which cause Trp308Cys in protein sequence was identified only in the proband and another affected member. LKB1 protein activity could be reduced due to changes in LKB1 protein conformation structure by Trp308Cys.</p><p><b>CONCLUSION</b>Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterised by mucocutaneous pigmentation, multiple gastrointestinal hamartomatous polyps and heredofamilial nature. Gene identification and mutagen screening of LKB1 gene in all PJS patients and first degree relatives will contribute to a definite diagnosis and improve the life span of the family.</p>

Mismatch repair gene hMLH1 A655G/A polymorphism and colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the etiological role of hMLH1 gene A655 polymorphism in colorectal cancer.</p><p><b>METHODS</b>A case-control study was carried out, including 115 colorectal cancer patients and 135 healthy people as control. Genomic DNA was extracted from peripheral white blood cell from all the subjects. Polymorphism was detected by PCR-based DHPLC analysis and verified by DNA sequencing.</p><p><b>RESULTS</b>The hMLH1 gene A655G polymorphism was detected in 3.0% of healthy people and 11.3% of colorectal cancer patients (P<0.01), and the difference was significant (P<0.01). The hMLH1 gene A655G polymorphism was detected in 8.2% of tubular adenocarcinoma or tubular-papillary adenocarcinoma and 27.8% of mucinous adenocarcinoma, which was also significant (P<0.05).Meanwhile, hMLH1 gene A655G polymorphism was not associated with age, gender and lymphatic metastasis (all P>0.05).</p><p><b>CONCLUSIONS</b>The hMLH1 gene A655G polymorphism may play a role in the pathogenesis of colorectal cancer. Determination of the polymorphism may be a potential marker to predict the prognosis of colorectal cancer patients.</p>

Association of IVS10+12G>A polymorphism in hMSH2 gene with colorectal cancer in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the single-nucleotide polymorphism (SNP) IVS10+12 G>A in hMSH2 gene with colorectal cancer in a Chinese population of Jiangsu province.</p><p><b>METHODS</b>A case-control study to investigate whether this SNP affects the risk of developing colorectal cancer was conducted. Subjects included 108 colorectal cancer patients and 180 healthy individuals. Peripheral white blood cell DNA was obtained from all subjects. The hMSH2 gene IVS10+12 G>A was genotyped using a PCR-based DHPLC, the existence of IVS10+12 G>A was verified by DNA sequencing.</p><p><b>RESULTS</b>The allele frequency of the IVS10+12 G>A in the hMSH2 gene in the healthy individuals was 51.7%. There was significant difference in the frequency of the IVS10+12 G>A between patients and healthy controls (P<0.05), and between familial patients and healthy controls (P<0.05). There was also significant difference of the frequency of the IVS10+12 G>A between patients younger than 50 years, and patients with high consumption of fried food and pickled vegetable and healthy controls respectively (P<0.05).</p><p><b>CONCLUSION</b>This SNP may be associated with colorectal cancers in Chinese. Further investigation with larger sample size is needed.</p>

Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli (APC) gene in 3 familial adenomatous polyposis (FAP) pedigrees and to screen large fragment deletions in the APC gene.</p><p><b>METHODS</b>DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR (MSP) and DNA sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene.</p><p><b>RESULTS</b>No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family.</p><p><b>CONCLUSION</b>Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.</p>

Germline mutation of adenomatous polyposis coli gene in Chinese patients with familial adenomatous polyposis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the characteristics of adenomatous polyposis coli (APC) gene germline mutations in Chinese patients with familial adenomatous polyposis (FAP).</p><p><b>METHODS</b>Eighteen members from nine FAP pedigrees were studied by using multiplex ligation-dependent probe amplification(MLPA) to detect large fragment deletion of APC gene. Then, PCR were performed to amplify all exons of APC gene for mutation screening by denaturing high performance liquid chromatography (DHPLC). When abnormal elution profile of DHPLC was found, DNA sequencing was performed to determine the mutations.</p><p><b>RESULTS</b>Mutations were identified in three pedigrees among the nine pedigrees. They were c.3184_3187 del CAAA in pedigree 2, c.5432C to T in pedigree 4 and c.3925_3929 del AAAAG in pedigree 9 respectively. Among them, c.5432C to T was novel.</p><p><b>CONCLUSION</b>APC gene germline mutations can cause the development of FAP. The FAP patients without APC gene germline mutations could be caused by other mechanisms.</p>

A novel APC gene germline mutation in a familial adenomatous polyposis pedigree / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the adenomatous polyposis coli (APC) gene germline mutation in the proband and her family members with familial adenomatous polyposis (FAP).</p><p><b>METHODS</b>The diagnosis of a patient with FAP was validated by colonoscopy, pathology and the family history. The systematic screening with multiplex ligation-dependent probe amplification (MLPA), denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing were carried out to detect APC gene germline mutations.</p><p><b>RESULTS</b>A novel mutation c.1999 C >T (Q667X) of APC, which leads to premature termination of the protein, was identified in this family. This mutation manifested an aggressive form of FAP with early onset of colorectal adenocarcinoma and colonic adenoma.</p><p><b>CONCLUSION</b>The mutation of APC Q667X is the cause of clinical phenotype of this family with FAP, and the prophylactic colectomy for the affected family members should be considered.</p>

The expression of mutation p53 gene from circulating cancer cells of peripheral blood and the clinical significance in detecting the patients with colorectal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the clinical significance of detecting p53 gene mutation expression in colorectal cancer cells of peripheral blood.</p><p><b>METHODS</b>Flow cytometry (FCM) was used to detect p53 gene mutation expression in peripheral blood cancer cells of 128 patients with colorectal cancer. Experimental data were analyzed by SPSS (v.11.0) software.</p><p><b>RESULTS</b>The lymph node metastasis showed the significant difference statistically (P<0.01) between p53 positive and negative expression in the colorectal cancer patients. The mutation p53 expression associated with existing histological differentiation (r=0.8476, P<0.05). A lymph node metastasis difference was observed between left and right colorectal cancers of mutation p53 positive expression.</p><p><b>CONCLUSION</b>Detecting the mutation p53 expression in cancer cells of peripheral blood might be helpful to the early diagnosis of colorectal cancer.</p>

Study of in vivo micronucleus formation in lymphocytes from the patients and its relation to malignant degrees of colorectal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the micronucleus (MN) formation in lymphocytes from patients with the malignant degrees of colorectal cancer.</p><p><b>METHODS</b>The MN test in capillary blood lymphocytes was conducted in 112 patients randomly selected from in-hospital patients before therapy. Experimental data were analyzed by SPSS (v.10.1) software.</p><p><b>RESULTS</b>The differences in the frequency of MN between 7 pathological types of colorectal cancers and controls were statistically significant (P<0.01). The frequency of MN increased with the decrease of the histological differentiation in colorectal cancer, and the statistically significant differences were seen between low differentiation group and the other differentiation groups in colorectal cancers.</p><p><b>CONCLUSION</b>There is a significant correlation between MN formation and the malignant degrees of colorectal cancer, and MN formation will be a useful biomarker for the identification of malignant degrees of colorectal cancer before operation or for the screening of high risk subgroup.</p>