Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colo-rectal cancer in young patients is a subject of interest for many reasons. Various studies are devoted to this subject but controversies regarding the stages, the evolution and the prognosis still remains. We present intermediate results, of an ongoing study, which is directed to those particular aspects of colon cancer of the patients less than 45 years of age in a region where the global incidence of the disease is one of the highest in the world. In the past five years, we have observed 602 patients with colon cancer. 23 of them (4%) were less than 45 years old. The age at diagnosis was 38 +/- 6 years. Two-thirds of the subjects were male. 13% had had predisposing conditions for colon cancer such as FAP, ulcerative colitis or Turcot syndrome; 50% had a positive familial history for cancer. Symptoms lasted for less than 3 months in two thirds of the patients. 15% had a right sided tumor, 38% were located in the sigmoid and 28.5% in the rectum. At diagnosis, the tumors were classified as follows: 32% Dukes B, 23% Dukes C and 40% were disseminated disease. Most of them were located in the rectum, but 43% of Dukes B lesions were located in ascending or transverse colon. Grading reveal moderately to poorly differentiated tumors in 3/4 of cases. 30% of patients received an adjuvant therapy. After two years, 70% of the patients were alive. None of them with Dukes A or B but one of the patients with Dukes C were dead.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Colorectal cancer before 45 years of age]. 164 6

Ras gene family (c-Ha, Ki, N ras) and c-myc proto-oncogenes were analyzed in seven colonic and three gastric adenomatous polyps obtained from a patient with Turcot's syndrome. The rearrangement and amplification as well as overexpression of c-Ha ras gene in one colonic adenomatous polyp were determined. The amplified c-Ha ras gene in this polyp revealed larger fragments of BamHI, PstI and SacI than those in the normal colonic mucosa from the same patient. But, such abnormalities were not observed in other polyps. No abnormalities of c-Ki ras, c-N ras or c-myc gene were observed in any polyps. These results suggest that the alternations of c-Ha ras gene in this patient may not be responsible for the adenomatous change, but may be related to the transition from adenoma to carcinoma of the colon.
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PMID:Rearrangement, amplification and overexpression of c-Ha Ras gene in premalignant lesion of Turcot's syndrome. 170 48

A retrospective study was carried out in nine children between the ages of 10 and 20 years with adenocarcinoma of the colon. No family history, significant medical history, or predisposing factors were identified, except for Turcot's syndrome in one child. Common presenting signs and symptoms were vague abdominal pain, nausea and vomiting, weight loss, change in bowel habits, and guaiac-positive stools. Five of the patients' diagnoses were delayed for an average of 11.6 months, the majority of whom had Dukes' D disease. Their median survival was 4 months compared with 24 months in the four patients diagnosed early. As with adults, the mainstay of therapy is operation. Our data indicate that an increased awareness and consideration of colon cancer in children will result in earlier diagnosis, a more favorable disease stage, and prolonged survival.
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PMID:Adenocarcinoma of the colon in adolescents. 320 57

Increased in vitro tetraploidy occurred in skin cultures derived from all affected patients and some family members at risk studied in families with heritable colon cancer syndromes (15 of 16 Gardner syndrome families, three Oldfield syndrome families, and four families with heritable colon cancer syndrome without polyposis coli) but was not present in all (one Gardner syndrome family, 16 of 19 familial polyposis coli families, and two Turcot syndrome families). Seven of 97 controls, family members by marriage, showed increased in vitro tetraploidy. None of these seven had a family history of colonic cancer but four had a family history of other solid tumors. Such in vitro studies illustrated that the occurrence of in vitro tetraploidy should be determined in families rather than individuals in order to determine whether all patients clinically affected show increased in vitro tetraploidy and vertical transmission that can be documented.
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PMID:Occurrence of in vitro tetraploidy in the heritable colon cancer syndromes. 728 60

Turcot syndrome is characterized by an association of malignant brain tumors and colon cancer developing in the patient's teens. Since the mechanism of carcinogenesis in Turcot syndrome is still unclear, we analysed genetic changes in tumors from a Turcot patient with no family history of the condition. All tumors, including one astrocytoma, three colon carcinomas, and two colon adenomas, exhibited severe replication error (RER), and all colon tumors showed somatic mutations at repeated regions of TGFbetaRII, E2F-4, hMSH3, and/or hMSH6 genes. Somatic APC mutations were detected in three of three colon carcinomas, and somatic p53 mutations were detected in the astrocytoma and two of three colon carcinomas, both of which showed two mutations without allele loss. We also found that normal colon mucosa, normal skin fibroblasts and normal brain tissue from this patient showed respective high frequencies of RER, in contrast to usual HNPCC patients in which RER was very rare in normal tissues. These results suggest that extreme DNA instability in normal tissues causes the early development of multiple cancer in Turcot syndrome. A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. Additional unknown germline mutation may contribute to the genetic instability in normal tissues.
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PMID:Drastic genetic instability of tumors and normal tissues in Turcot syndrome. 941 79

Typical Turcot's syndrome is characterized by the association of a brain glioma together with multiple colonic polyposis, in which the number of polypoid lesions is small and the association of colonic cancer occurs at a younger age than in familial adenomatous polyposis. We describe a family in which both the father and his son presented with typical Turcot's syndrome without parental consanguinity. This is the first report of a family that is considered to follow an autosomal dominant inheritance. After reviewing 25 documented cases in which the average age of death was 20.3 years old, it was learned that the major cause of death was brain tumor (76 percent) and the minor cause was colon cancer (16 percent). Patients were very young and, therefore, unlikely to have produced a child before their death. These facts seem to support the theory that Turcot's syndrome is an autosomal dominant disorder.
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PMID:A father and son with Turcot's syndrome: evidence for autosomal dominant inheritance: report of two cases. 1021 61

A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.
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PMID:Ganglioglioma in a patient with Turcot syndrome. Case report. 1061 98

Rare inherited syndromes that to some extent explain familial glioma include Turcot's syndrome, Li-Fraumeni syndrome and neurofibromatosis types I and II. The majority of families with glioma do not meet the clinical criteria for any of these syndromes. In order to study the genetic origin of familial glioma, tumour DNA (n = 35) or blood samples (n = 8) were collected from 25 families. The glioma tumours were tested for microsatellite instability (MSI) with two markers, BAT25 and BAT26, since glioma is associated with hereditary non-polyposis colon cancer (HNPCC) in Turcot's syndrome. Furthermore, p53 was screened from blood DNA (exons 2-11) with temporal temperature gradient electrophoresis (TTGE) since germline mutations in p53 are seen in Li-Fraumeni syndrome. In gliomas, there is a wide variety of somatic mutations, such as, for instance, in p53, the epidermal growth factor receptor (EGFR) and p16. The tumour suppressor gene PTEN is also often somatically mutated in glioma, therefore it is attractive as a candidate gene for germline mutations in familial glioma. Blood DNA was directly sequenced for mutations in PTEN exons 1-9. The analysis showed that no mutations were found in either of the studied tumour suppressor genes, and no MSI-positive tumours were found. A common polymorphism in p53 at codon 72 (arginine/proline) was found in 6/8 of the patients. Apparently, mutation in the tested tumour suppressor genes or DNA mismatch repair genes does not explain the familial glioma observed in these families.
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PMID:Microsatellite instability, PTEN and p53 germline mutations in glioma families. 1166 37

Medulloblastoma is a malignant, invasive embryonal tumour of the cerebellum which manifests preferentially in children. A subset of cases is associated with colon cancer and APC germline mutations (Turcot syndrome), and APC and beta-catenin point mutations occur in up to 10% of sporadic cases, indicating the involvement of the Wnt pathway in the development of medulloblastoma. In 39 sporadic cerebellar medulloblastomas screeened for alterations in the AXIN1 gene, another component of the Wnt pathway, we found missense AXIN1 mutations in two tumours, CCC-->TCC at codon 255 (exon 1, Pro-->Ser) and TCT-->TGT at codon 263 (exon 1, Ser-->Cys). Furthermore, the A allele at the G/A polymorphism at nucleotide 16 in intron 4 was significantly over-represented in medulloblastomas (39 cases; G 0.76 vs-A 0.24) compared to healthy individuals (86 cases; G 0.91 vs A 0.09; P=0.0027). RT-PCR revealed large deletions in the AXIN1 gene in 5/12 (42%) medulloblastomas, consistent with a previous report. However, we observed such deletions at a similar frequency also in normal brain tissue (6/12, 50%). Since there are multiple complementary, inverted sequences present in the AXIN1 gene, these large deletions may represent RT-PCR errors due to stem-loop secondary structures.
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PMID:AXIN1 mutations but not deletions in cerebellar medulloblastomas. 1255 76

Germline mutations of APC in patients with Turcot syndrome (colon cancer and medulloblastoma), was well as somatic mutations of APC, beta-catenin, and Axin in sporadic medulloblastomas (MBs) have shown the importance of WNT signaling in the pathogenesis of MB. A subset of children with MB have germline mutations of SUFU, a known inhibitor of Hedgehog signal transduction. A recent report suggested that murine Sufu can bind beta-catenin, export it from the nucleus, and thereby repress beta-catenin/T-cell factor (Tcf)-mediated transcription. We show that an MB-derived mutant of SUFU has lost the ability to decrease nuclear levels of beta-catenin, and cannot inhibit beta-catenin/Tcf-mediated transcription as compared to wild type SUFU. Our results suggest that loss of function of SUFU results in overactivity of both the Sonic Hedgehog, and the WNT signaling pathways, leading to excessive proliferation and failure to differentiate resulting in MB.
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PMID:Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling. 1507 59


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