Cases reported "Genomic Instability"

Filter by keywords:



Retrieving documents. Please wait...

1/9. Genomic imbalance and onco-protein expression of ovarian endometrioid adenocarcinoma arisen in an endometriotic cyst.

    BACKGROUND: Malignant transformation in endometriosis is a rare but well known complication. However, detailed mechanisms of malignant transition and tumourigenesis in endometriosis remain unknown. We here describe the case of an endometrioid carcinoma arisen in endometriotic ovarian cyst fulfilling Sampson's criteria for malignant transformation of endometriosis. We compared genetic alterations and oncoprotein expression in the endometriotic ovarian cyst and the associated endometrioid adenocarcinoma. MATERIALS AND methods: genomic instability was evaluated by comparative genomic hybridization (CGH). Onco-protein expression was analysed by immunohistochemistry with antibodies against bcl-2, c-MYC, cyclin d1, p53, HER-2 and KIT protein. RESULTS: CGH revealed a gain of 8q, including the locus of the oncogene c-MYC at 8q24. immunohistochemistry disclosed a differing protein expression profile between the epithelia of the pre-existing cyst and adenocarcinoma. Apart from HER-2, all onco-proteins were more strongly expressed in epithelial cells of the adenocarcinoma than of the endometriotic cyst. CONCLUSION: The solitary genomic imbalance of chromosome 8 possibly reflects the importance for initiation and/or progression of endometrioid carcinoma. Overexpression of onco-proteins then may occur subsequently in the malignant transformation of ovarian endometriosis. However, the exact mechanisms of malignant transition in ovarian endometriosis remain to be elucidated in future studies with a higher number of cases. ( info)

2/9. Molecular analysis of astrocytoma associated with Turcot syndrome type 1--case report.

    A 49-year-old man presented with a brain tumor and colon carcinoma. The patient had been treated under diagnoses of hereditary non-polyposis colorectal cancer syndrome and muir-torre syndrome. magnetic resonance imaging revealed a mass lesion in the right frontal lobe with diffuse high intensity on T2-weighted and fluid-attenuated inversion recovery images. A few small lesions were enhanced by gadolinium on the T1-weighted images. Histological examination revealed the brain neoplasm was astrocytoma grade III according to the world health organization classification. Molecular genetic analysis detected microsatellite instability and p53 mutation only in the tumor tissue, indicating a failure of the deoxyribonucleic acid mismatch repair system. These results suggest that inactivation of mismatch repair system and p53 is closely associated with the tumorigenesis of this neoplasm. The final diagnosis was Turcot syndrome type 1. ( info)

3/9. First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability.

    The NBS1 gene is strongly linked to several factors involved in genome integrity. Functional disruption of NBS1 could therefore induce genomic instability and carcinogenesis. Four children with acute lymphoblastic leukemia have been reported to be heterozygous for a germline and/or somatic missense mutation in NBS1, leading to the I171V substitution. We screened healthy controls and pediatric patients with hematological malignancies and aplastic anemia (AA) for the presence of I171V. Of the 62 patients, one individual with AA was confirmed to harbor a homozygous I171V mutation. Genetic analysis of NBS1 in this patient and her healthy parents indicated that she inherited the germline I171V mutation from her father and the wild-type allele from her mother, and that the second I171V hit occurred on the wild-type allele early in embryonic development. Furthermore, cytogenetic analysis of lymphoblastic cell lines from the patient indicated a remarkable increase in numerical and structural chromosomal aberrations in the absence of clastogens, suggesting that she potentially carried genomic instability. This is the first report of AA with a homozygous I171V mutation. We hypothesize that NBS1 may play an important role in the pathogenesis of AA. ( info)

4/9. A case of osteoclast-type giant cell tumor of the pancreas with high-frequency microsatellite instability.

    It has been reported that osteoclast-type giant cell tumor of the pancreas (OGTP) is rare, with a frequency of only 0.2% of the total reported pancreatic carcinomas. We report herein a rare case of OGTP in a 57-year-old Japanese man. Preoperative examinations showed a solid and cystic tumor, measuring 20 x 15 cm at the pancreas body. The resected specimen was a solid tumor with a giant cyst containing bloody contents. The tumor was composed of a proliferation of mononuclear cells admixed with osteoclast-type giant cells. The tumor cells were immunoreactive for vimentin, alpha1-antitrypsin, and EMA but not for CEA and cytokeratin. These findings indicated that this case was a malignant OGTP. The tumor cells showed microsatellite instability with high frequency (MSI-H). The present patient is alive 3 years after the operation, while OGTP has been reported to have a poor outcome. It has been reported that pancreatic carcinomas with MSI-H status have a favorable outcome. MSI-H might be one of the predictive markers for the long survival in OGTP. ( info)

5/9. Interstitial 6q deletion: clinical and array CGH characterisation of a new patient.

    We report on a patient with an interstitial 6q deletion presenting with moderate mental retardation, persisting hypotonia, facial dysmorphism, but no internal malformations. Standard cytogenetic analysis identified a de novo interstitial 6q deletion. Molecular karyotyping using a 1 Mb array estimated the size of the deletion at approximately 14 Mb encompassing band q16 of chromosome 6. This case report illustrates how the molecular delineation enables improved genotype-phenotype correlations of chromosomal abnormalities to be made and may improve medical care and genetic counselling in individuals with chromosomal imbalances. ( info)

6/9. AGG interspersion analysis of the FMR1 CGG repeats in mental retardation of unspecific cause.

    OBJECTIVES: To study the AGG interspersion pattern in mentally retarded patients of unspecified cause. methods: FMR1 CGG substructure in 104 normal and 232 mentally retarded (MR) males was determined by CGG repeat and AGG interspersion analyses. Genomic dna of the study subjects was obtained for PCR and Southern hybridization analyses. RESULTS: All study subjects had less than 53 CGG repeats and none had fragile x syndrome of mental retardation. There was a significant difference (P < 0.006) in the AGG interspersion pattern. MR males had (1) more variable internal substructures, (2) proportionally less 2 and 3 AGG but more 0 and 1 AGG, less (CGG)(9)AGG(CGG)(9)AGG(CGG)(9) but more (CGG)(9)AGG(CGG)(19) alleles and (3) a longer pure 3' CGG repeat. CONCLUSIONS: Our results suggest that the MR alleles have a lesser number of interspersed AGG and a longer pure 3' CGG repeat than the normal population. They are thus more prone to instability and expansion to long repeat lengths as in the fragile x syndrome of mental retardation. ( info)

7/9. Small bowel adenocarcinoma with high levels of microsatellite instability in Crohn's disease.

    microsatellite instability (MSI) is a hallmark of carcinomas occurring in the setting of hereditary nonpolyposis colorectal cancer, but can also be found in sporadic and colitis-associated tumors. The incidence of MSI in Crohn's disease is unknown and has usually been reported in the colon. We report the case of a 26-year-old man, diagnosed 4 years earlier with Crohn's disease, who developed an associated small bowel adenocarcinoma. The tumor was found to have high levels of MSI by immunohistochemical staining and by MSI testing. No mutations were identified by genetic testing, and high levels of MSI are most probably due to hypermethylation. ( info)

8/9. A novel MLH1 mutation harbored as a germ line aberration by a young woman of an HNPCC-like family and exhibited by a CML patient when occurring prior to the initiation of the blast phase concomitant with a c-MYC amplification.

    Germ line mutations in the MLH1 and MSH2 genes account for the majority of hereditary nonpolyposis colorectal cancer (HNPCC) families. Here, we describe a family that does not meet the international criteria for HNPCC, of which a young woman harbors a missense mutation (D132H). This novel germ line mutation has not previously been reported. Of the mismatch repair (MMR) genes, MLH1 has been shown to play an important role in hematologic malignancies. The novel mutation was also revealed to be a somatic aberration occurring prior to the initiation of the blast phase in a chronic myelogenous leukemia (CML) patient. Among the possible MLH1 partners involved in signaling MMR or apoptosis is the proto-oncogene c-MYC, which is closely related to cellular proliferation. We further revealed a concomitant c-MYC dramatic amplification in the CML-MLH1-mutation carrier patient, also occurring at the pre-blast phase. Our data contribute further to characterizing the mutational spectrum of the MLH1 gene. Furthermore, given the role of c-MYC and its interaction with MLH1, taken together with the mutational status of both genes revealed at the pre-blast phase in the CML patient, a plausible increased genetic instability might be expected to take place, possibly contributing to blast triggering. Our results may provide additional insight into the complex interplay between the MMR system and other cellular pathways. ( info)

9/9. Collision tumor of the rectum: a case report of metastatic gastric adenocarcinoma plus primary rectal adenocarcinoma.

    Collision tumors are thought to arise from the accidental meeting and interpenetration of two independent tumors. We report here a highly unusual case of a 61-year old man who had a unique tumor that was composed of a metastatic adenocarcinoma from the stomach to the rectum, which harbored a collision tumor of primary rectal adenocarcinoma. The clonalities of the two histologically distinct lesions of the rectal mass were confirmed by immunohistochemical and molecular analysis. Although histologic examination is the cornerstone in pathology, immunohistochemical and molecular analysis can provide evidence regarding whether tumors originate from the same clone or different clones. To the best of our knowledge, this is the first reported case of such an occurrence. ( info)


Leave a message about 'genomic instability'


We do not evaluate or guarantee the accuracy of any content in this site. Click here for the full disclaimer.