Cumulative dosage effect of a RAD51L1/HMGA2 fusion and RAD51L1 loss in a case of pseudo-Meigs' syndrome.

Uterine leiomyoma presenting with ascites and pleural fluid is referred to as pseudo-Meigs' syndrome. It is unclear whether common uterine leiomyomas and uterine leiomyomas causing pseudo-Meigs' syndrome are cytogenetically related or whether functionally different primary pathogenetic triggers are responsible for the differences in tumor phenotype. In this study, we investigated the possible involvement of RAD51LI and HMGA2 (formerly known as HMGIC) in initiation and/or progression of a huge uterine leiomyoma presenting as pseudo-Meigs' syndrome. The detailed cytogenetic and FISH analysis revealed the presence of two subclones with a complex karyotype, 46,XX,t(2;12)(q31;q21),ins(14;12)(q23-24;q15q21).ish del(12)(q15q15) (LL12NC01-142H1-,LL12NC01-27E12-),der(12)t(2;12)(LL12NC01-142H1+,LL12NC01- 27E12-),der(14)ins(14;12)(q22;q15q15) (LL12NC01-142H1+,LL12NC01-27E12+,RAD51LI+), der(14)ins(14;12)(q23-q24;q15q21) (LL12NC01-142H1-, LL12NC01-27E12+) [20]/46,idem,del(14)(q21q24).ish(RAD51LI-) [6], indicating intragenic HMGA2 rearrangement and loss of one of the RAD51LI alleles in a derivative subclone with chromosome 14 deletion. Furthermore, RACE and RT-PCR analysis of the tumor cells did not reveal abnormal HMGA2 or RAD51LI transcripts. Additionally, the cellular subclone with intrachromosomal 14q21-q24/RAD51LI deletion showed an in vitro growth advantage over the subclone without the deletion. This observation supports a model in which accumulation of two independent mutations-a classical structural rearrangement involving HMGA2 and RAD51L1, in combination with a loss of the second RAD51L1 allele-might play a major role in the development of pseudo-Meigs' syndrome

Does conventional cytogenetics detect the real frequency of 19q13 aberrations in benign thyroid lesions? A survey of 38 cases.

Item does not contain fulltextStructural aberrations involving chromosomal band 19q13.4 are examples of clonal cytogenetic deviations that have been detected in subgroups of follicular thyroid adenomas and goiters. About 45% of the adenomas and 8% of the goiters showed clonal aberrations, about 20% of which involve 19q13. The aberrations are translocations with a remarkable variation of the translocation partners of chromosome 19. Considering that structural changes involving small chromosome segments do not always have a characteristic band to be accurately identified, one may assume an even higher rate of these aberrations in thyroid lesions. To detect hidden 19q13 translocations, we performed fluorescence in situ hybridization analyses with a subtelomeric 19q specific probe on a subset of 38 thyroid adenomas with an apparently normal karyotype. No hidden chromosome abnormality was detected in our study, indicating that conventional cytogenetics reflects the true percentage of 19q13 aberrations in follicular thyroid adenomas

Identification of oligodendroglioma specific chromosomal copy number changes in the glioblastoma MI-4 cell line by array-CGH and FISH analyses.

Item does not contain fulltextGlioblastomas, the most frequent and malignant glial tumors, are known to be phenotypically heterogeneous. A low fraction of glioblastomas is associated with specific chromosomal losses at 1p and 19q, which are commonly found in oligodendrogliomas and are generally considered to be a primary event in the development of these tumors. Subsequent progression of oligodendroglial tumors appears to be triggered by additional molecular features underlying the transition to anaplastic oligodendroglioma and glioblastoma multiforme (GBM) such as deletions of 9p and 10q, and alterations of CDKN2A (p16), which is located at 9p21. These findings strengthen the view that GBM on rare occasions may develop from oligodendroglial differentiated cells. In the present study, we evaluated the newly established MI-4 glioblastoma cell line, which displays 1p and 19q specific alterations targeting preferential regions of allelic loss in glial neoplasms, by array-CGH and fluorescence in situ hybridization (FISH) analyses that were combined to obtain a high resolution map of targeted chromosome rearrangements and copy number changes throughout the genome. Genome-wide and chromosome 19 full coverage array-CGH analysis of the MI-4 cell line revealed that in this particular cell line, 1p-specific loss, including the CDKN2 (p18) gene, is not accompanied by loss of the previously described 19q13.3 tumor suppressor candidate region. Interestingly, the array-CGH (CGHa) profile showed an increase in copy number along most of 19q including the AKT2 oncogene and the KLKs gene family, which have previously been shown to be amplified in pancreatic carcinomas and upregulated in several tumors, respectively. The concomitant 1p partial loss and chromosome 19 alterations, with the +7 and -10-specific GBM markers associated with homozygous deletion of 9p21.3 including CDKN2A (p16), are distinct features of the glioblastoma MI-4 cell line, illustrating its origin from an olidodendroglial tumor. Based on these results, we conclude that the MI-4 glioblastoma cell line might function as a model system for investigations into the behavior of a defined oligodendroglioma subtype

Molecular cytogenetic definition of three distinct chromosome arm 14q deletion intervals in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms characterized by frequent chromosome arm 14q losses. In this study, the 14q changes in a series of 39 histologically and immunohistochemically confirmed GISTs were analyzed in detail by metaphase and/or interphase fluorescence in situ hybridization (FISH) studies using 21 genetically well-characterized, region-specific 14q11-24 YAC clones. By conventional cytogenetic analysis, acquired clonal chromosome aberrations were found in 17 out of 35 tumors. Chromosome 14 was involved in 13 cases; six specimens showed complete chromosome 14 loss, while the remaining seven had structural abnormalities with the breakpoints residing within the intervals 14q11-13 or 14q22-24. Other recurrent chromosome aberrations included frequent deletions of chromosome 1p (11/17), losses of chromosome 22 (7/17), losses or deletions of chromosome arm 13 (6/17) or 15 (4/17), and gains or translocations involving chromosome 17 (4/17). Combining cytogenetic data with double-color FISH analysis, total or partial losses of 14q material were detected in 29 out of 36 tumors (81%). The 14q losses were found in all stages and histological subtypes. Two most frequent common deletion regions flanked by YACs 931B1 and 761D4, and 802E7 and 892C11 at 14q23-24 (25/30 of each; 83%) could be identified. Furthermore, 21 tumors (70%) shared a region of deletion defined by YACs 957H10 and 931E5 at 14q11-12. Our results suggest the presence of at least three distinct critical deletion regions on chromosome 14 in GISTs

Molecular cytogenetic definition of three distinct chromosome arm 14q deletion intervals in gastrointestinal stromal tumors.

Item does not contain fulltextGastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms characterized by frequent chromosome arm 14q losses. In this study, the 14q changes in a series of 39 histologically and immunohistochemically confirmed GISTs were analyzed in detail by metaphase and/or interphase fluorescence in situ hybridization (FISH) studies using 21 genetically well-characterized, region-specific 14q11-24 YAC clones. By conventional cytogenetic analysis, acquired clonal chromosome aberrations were found in 17 out of 35 tumors. Chromosome 14 was involved in 13 cases; six specimens showed complete chromosome 14 loss, while the remaining seven had structural abnormalities with the breakpoints residing within the intervals 14q11-13 or 14q22-24. Other recurrent chromosome aberrations included frequent deletions of chromosome 1p (11/17), losses of chromosome 22 (7/17), losses or deletions of chromosome arm 13 (6/17) or 15 (4/17), and gains or translocations involving chromosome 17 (4/17). Combining cytogenetic data with double-color FISH analysis, total or partial losses of 14q material were detected in 29 out of 36 tumors (81%). The 14q losses were found in all stages and histological subtypes. Two most frequent common deletion regions flanked by YACs 931B1 and 761D4, and 802E7 and 892C11 at 14q23-24 (25/30 of each; 83%) could be identified. Furthermore, 21 tumors (70%) shared a region of deletion defined by YACs 957H10 and 931E5 at 14q11-12. Our results suggest the presence of at least three distinct critical deletion regions on chromosome 14 in GISTs

Intragenic breakpoint within RAD51L1 in a t(6;14)(p21.3;q24) of a pulmonary chondroid hamartoma.

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Endometrial stromal sarcoma presenting as postpartum haemorrhage: report of a case with a sole t(10;17)(q22;p13) translocation.

Item does not contain fulltextBACKGROUND: Although the clinical picture of endometrial stromal sarcoma (ESS) is variable, it was never reported to present as a postpartum hemorrhage. In addition, ESS is a tumor type of which, due to its rarity, little is known regarding chemosensitivity and genetic changes. CASE: A 28-year-old woman complaining of persistent postpartum bleeding was referred to our hospital, where she was diagnosed with ESS. At laparotomy, the invasion of nervous and vascular pelvic structures rendered her inoperable, and chemotherapy (doxorubicin 50 mg/m(2) for 15 min; ifosfamide 5 g/m(2)/24 h; mesna 5 g/m(2), every 3 weeks) was initiated. The ESS appeared to be chemosensitive because after three treatment cycles the tumor iliac metastase significantly decreased in volume and became surgically removable. Chemosensitivity was confirmed microscopically. Three additional courses of chemotherapy and pelvic irradiation were administered. Cytogenetic evaluation of both the primary as well as the metastatic lesions revealed a t(10;17)(q22;p13) as the sole cytogenetic abnormality. CONCLUSIONS: Three interesting features of this particular case put ESS in a new perspective. First, the fundal ESS permitted normal conception and pregnancy but caused a postpartum haemorrhage. Second, the ESS was clearly chemosensitive. Third, we report a novel cytogenetic aberration in ESS, the molecular characterization of which might lead to the identification of the deregulated pathway(s) triggering tumor development in ESS

Ethnic variations in uterine leiomyoma biology are not caused by differences in myometrial estrogen receptor alpha levels.

Item does not contain fulltextOBJECTIVE: Uterine leiomyomas develop in women of reproductive age and regress after menopause, suggesting that they grow in a steroid hormone-dependent fashion. Furthermore, it is widely accepted that symptomatic uterine leiomyomas occur at a twofold to threefold higher frequency in black women than in white women. The present study was designed to investigate a possible physiologic role of racial differences in the myometrial estrogen receptor alpha in this phenomenon. METHODS: We compared the expression of the estrogen receptor and progesterone receptor in myometrium by ligand-binding assay and the estrogen receptor alpha by real-time polymerase chain reaction in women from different ethnic backgrounds who have uterine leiomyoma. RESULTS: Estrogen receptor and progesterone receptor concentrations and estrogen receptor alpha transcription levels were not statistically different between ethnic backgrounds. CONCLUSION: Neither on a transcriptional nor on a protein level were there statistically relevant differences in steroid hormone receptor levels. A causative role for these receptors in the ethnic variation of leiomyoma biology seems unlikely

Intragenic breakpoint within RAD51L1 in a (6;14) (q21.3;q24) of a pulmonary chondroid hamartoma

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