1/13. The hPMS2 exon 5 mutation and malignant glioma. Case report.patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome 1p. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is not commonly involved in sporadic oligodendrogliomas or glioblastomas.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
2/13. Genetic susceptibility for specific cancers. Medical liability of the clinician.The use of genetic profiling techniques to detect individuals with an increased susceptibility to heritable cancers has provoked recent legal interest in the duties of the attending physician and in the rights of patients and their families. In the current study specific prima facie and recently litigated cases are presented and explored to delineate the issues facing physicians and to illustrate the prerogatives of patients who are caught up in a heritable cancer enigma. Various courts have attempted to answer questions involving lawsuits in which incidents of breast/ovarian carcinoma and colon carcinoma have provoked claims of negligence against health care providers. health care workers involved in the care of these patients have specific duties to these individuals. It would appear that physicians are being forced to assume the additional duty of delving into a patient's family history of cancer through multiple generations. This duty is followed by a responsibility to provide detailed counseling to those patients in whom such activity impacts the diagnosis and management of familial cancer.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
3/13. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk.Increased intestinal permeability to several specific molecular probes has been observed in patients with Crohn's disease and their first-degree relatives. A positive family history is also a potent risk factor for inflammatory bowel disease. Although it has been argued that increased permeability in relatives may confer an increased future risk of developing Crohn's disease, long-term follow-up of such family members has been lacking. We describe a 24-year-old woman with a positive family history of Crohn's disease who had an elevated gut permeability to (51)Cr-EDTA at age 13, as part of a cross-sectional cohort study in patients and their first-degree relatives. She was asymptomatic at the time, and extensive investigation found no evidence of microscopic or macroscopic Crohn's disease. Repeat investigation because of symptom onset at age 21 revealed ileocolonic Crohn's disease, which required treatment with systemic corticosteroids to induce a clinical remission. In this case, a permeability defect was clearly identified to precede the onset of Crohn's disease in a subject at increased risk. This observation provides support for the hypothesis that increased gut permeability to macromolecules is an early step in the pathogenesis of this disorder.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
4/13. Familial microscopic colitis.Collagenous and lymphocytic colitis are two inflammatory conditions of the colon that are often collectively referred to as microscopic colitis. The present report describes what is believed to be the third published case of familial microscopic colitis. A 55-year-old woman who suffered from chronic diarrhea was diagnosed with lymphocytic colitis on colonic biopsy. Subsequently, her 36-year-old daughter was diagnosed with collagenous colitis. The familial occurrence of these diseases may support an immunological hypothesis for their etiology. In addition, it supports the assumption that collagenous and lymphocytic colitis are two manifestations of the same disease process rather than two completely separate entities. The familial tendency of this disease may make a case for early colonoscopy and biopsy in relatives of patients diagnosed with microscopic colitis if they present with suggestive symptoms.- - - - - - - - - - ranking = 3keywords = colon (Clic here for more details about this article) |
5/13. CDKN2A novel mutation in a patient from a melanoma-prone family.CDKN2A is thought to be the main candidate gene for melanoma susceptibility. Deletion or mutations in the CDKN2A gene may produce an imbalance between functional p16 and cyclin d, causing abnormal cell growth. We here describe a novel mutation consisting of a 1 bp deletion at nucleotide position 201 (codon 67) (CACGGcGCG) resulting in a truncated protein (stop codon 145). The patient, a female subject from a melanoma-prone family, presented at the age of 47 years with a superficial spreading melanoma of the trunk. Her father had colon cancer at the age of 43 years and melanoma at 63 years, her uncle suffered from gastric cancer, and her grandfather had laryngeal cancer.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
6/13. Investigations on a clinically and functionally unusual and novel germline p53 mutation.This report describes an individual with a rare choroid plexus papilloma in adulthood (age 29) after earlier having an osteosarcoma (age 22). The results from this study, and others, suggest that it may be advisable to consider the possibility of a germline p53 mutation in adults presenting with choroid plexus tumours. In the current study automated dna sequencing of genomic dna detected a novel germline 7 base pair insertion in exon 5 of the p53 gene in this patient. The alteration in frame would produce amino acid substitutions beginning with alanine to glycine at position 161 and a stop codon at position 182 in the mutated protein. Surprisingly two assays of p53 function gave apparently wild-type results on peripheral blood lymphocytes from this individual. These results led us to carry out more detailed functional tests on the mutant protein. The mutant allele was expressed either at very low levels or not at all in phytohaemagglutinin stimulated lymphocytes. Further, the mutant protein was completely non-functional in terms of its ability to transactivate a series of p53-responsive genes (p21(WAF1), bax, PIG3), to transrepress a target gene and to inhibit colony growth in transfected Saos-2 cells. However, surprisingly, data from irradiated peripheral blood lymphocytes and transfected Saos-2 cells, suggested that this truncated, mutant protein retains significant ability to induce apoptosis.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
7/13. A case of pulmonary adenocarcinoma accompanied by superior vena caval thrombosis in a patient with peutz-jeghers syndrome.A case of lung adenocarcinoma and extensive deep vein thrombosis in a patient with peutz-jeghers syndrome (PJS) is presented. A 31-year-old Chinese man complained of shoulder pain and swelling of the right arm. A series of diagnostic procedures revealed a primary adenocarcinoma in the left upper lobe with cervical and supraclavicular lymph node metastases accompanied by deep vein thrombosis in the superior vena cava and right jugular vein. In addition, typical pigmentation of the lips and oral mucosa and multiple hamartomas in the stomach, duodenum and colon led to the diagnosis of PJS. PJS is known to be associated with increased risk of malignancies, especially in the gastrointestinal tract, breast, genitals and pancreas. As bronchoscopic examination showed no hamartomatous lesions in the bronchi, the development of primary lung cancer in this young patient might be independent of any hamartomatous lesion and might be associated with some genetic factors relating to PJS.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
8/13. birt-hogg-dube syndrome.We present three members of a queensland family with clinical and histopathological features consistent with birt-hogg-dube syndrome. Two of the three family members were able to be screened for associated disorders. The mother of the family was found to have a solitary colonic polyp, a large ovarian cyst and two chorioretinal scars. No associated disorders were found on investigation of one of the two affected sons.- - - - - - - - - - ranking = 1keywords = colon (Clic here for more details about this article) |
9/13. A prospective study of the clinical, genetic, screening, and pathologic features of a family with hereditary mixed polyposis syndrome.In 1997, hereditary mixed polyposis syndrome (HMPS) was described in an Ashkenazi pedigree having colorectal polyps with mixed histology and risk for colorectal cancer (CRC). The mutation is now localized to 15q13-14. Since 1980, compliant relatives of an HMPS family were seen annually, tested genetically, and had colonoscopy offered every 1 to 2 yr from age 20 yr. The Israeli pedigree has 37 members (17 clinically affected by CRC or polyps), and seven of 13 available relatives entered our screening program. The others, followed-up elsewhere, provided clinical information. Half of our screened group had rectal bleeding; others were asymptomatic. colonoscopy, performed a mean of four times, identified polyps in all seven patients (mean age 28 yr). polyps were removed and included juvenile adenomas, mixed juvenile adenomas, hyperplastic polyps, mixed hyperplastic adenomas, serrated adenomas, and tubular adenomas. None of our screened patients developed CRC or extracolonic neoplasia. Linkage analysis localized their mutation to 15q13-14. This high-penetrance founder mutation so far is described only in Ashkenazim. The CRC pathway seems to be through juvenile and hyperplastic polyps. Mutation identification will aid screening for and evaluation of HMPS prevalence in Jewish and non-Jewish populations. Meanwhile, a cancer pedigree and correct classification of polyps will identify HMPS families. They require early and frequent colonoscopy, polypectomy, and elective extensive colectomy when indicated.- - - - - - - - - - ranking = 3keywords = colon (Clic here for more details about this article) |
10/13. Management of spontaneous colonic perforation in ehlers-danlos syndrome type IV.A 14-year-old girl with a family history of fatal colonic rupture, presented with a 2-day history of abdominal pain and signs of peritonitis. At laparotomy, a full-thickness perforation of the sigmoid colon was found, which was exteriorized as a loop colostomy. Subsequently, molecular studies of the patient's cultured fibroblasts found a point mutation in the COL3A1 gene, confirming a diagnosis of ehlers-danlos syndrome type IV (EDS-IV). Four and a half years later, a total abdominal colectomy and ileoproctostomy were performed, restoring intestinal continuity. At 5 years follow-up, the patient has had no further complications. Although spontaneous colonic perforation is a well-reported manifestation of EDS-IV, a consensus on the surgical management of this complication in EDS-IV has yet to be determined. Given the high rate of reperforation in EDS-IV when the colon is left in place and the low incidence of reported small bowel and rectal perforations, subtotal colectomy is a reasonable treatment. Primary anastomosis and avoidance of an end-ileostomy was possible in this young patient, with no evidence of anastomotic leakage nor reperforation to date. Lifelong close follow-up should be continued in these patients, because the natural history of this anatomy in EDS-IV is not known.- - - - - - - - - - ranking = 8keywords = colon (Clic here for more details about this article) |
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