RESUMO
Pelvic exenteration, first described in 1948 and subsequently refined, may be offered as a last hope of cure to patients with recurrent or locally advanced pelvic tumours, where radiotherapy is not an option. It is a complex, morbid, ultra-radical procedure involving en-bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid. This article discusses the evolution of and current indications for pelvic exenteration in gynaecologic oncology as well as the reasons for its decline: primary and secondary prevention of cervical cancer (the recurrence of which is the most common indication for exenteration); improvements in treatment of cervical, endometrial, vaginal and vulvar cancer in the primary and recurrent setting; and the advent of novel therapies.
Assuntos
Neoplasias dos Genitais Femininos , Exenteração Pélvica , Radioterapia (Especialidade) , Neoplasias do Colo do Útero , Neoplasias Vulvares , Humanos , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Neoplasias Vulvares/radioterapia , Neoplasias Vulvares/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Estudos RetrospectivosRESUMO
Because genes of the high mobility group protein family HMGI(Y) are known to take part in the development of a variety of benign solid tumors, the aim of the present study was to search for further members of that family in the human genome. Analysis for HMGI(Y)-related sequences by the polymerase chain reaction (PCR) with the use of cDNA-specific primers offered evidence for HMGIY-like sequences, whereas HMGIC-related sequences were apparently absent. By chromosomal assignment of somatic cell hybrids PCR, HMGIY cDNA-related sequences were detected on seven chromosomes. Positive clones were obtained by screening of a P1-derived artificial chromosome library and mapped by fluorescence in situ hybridization. One of these clones assigned to Xp22.1 was chosen for further analysis because Xp22 is a target region for clonal aberrations in benign solid tumors. Sequence analysis of a DNA fragment of this clone, designated as HMGIYL1, revealed a 94.4% homology to the coding region of HMGIY. Within the HMGIYL1 sequence, no nucleotide sequence divergences leading to a frame shift or a new termination codon compared to HMGIY were found, and a TATA-box-like motif 5' of it was detected. By reverse transcriptase PCR experiments with the use of HeLa cells and human fetal tissue, HMGIYL1 expression was not detectable. Nevertheless, if not active by itself, it is possible that HMGIYL1 may become activated by chromosomal rearrangements of Xp22 observed in benign solid tumors.
Assuntos
Aberrações Cromossômicas , Proteínas de Grupo de Alta Mobilidade/genética , Leiomioma/genética , Neoplasias Uterinas/genética , Cromossomo X , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , DNA de Neoplasias , Feminino , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Pulmonary chondroid hamartomas (PCHs) are benign mesenchymal tumors that often are characterized by specific chromosomal aberrations. Herein we report our cytogenetic and molecular cytogenetic (FISH) studies on 191 PCHs, including 48 previously published cases. In this series, 134/191 PCHs (70.2%) showed either abnormalities of chromosomal bands 6p21 (21 tumors), 12q14-15 (95 tumors), or had other abnormalities (18 tumors). Two tumors had a 6p21 aberration together with a 12q14-15 aberration. The most frequent translocations were t(12;14)(q15;q24) (19 cases) and t(6;14)(p21. 3;q24) (18 cases), both in either simple or complex form. By FISH with cosmids spanning the gene encoding the high-mobility-group protein HMGIC, we were able to show a rearrangement within or close to HMGIC in all tumors with 12q14-15 abnormalities tested, in 11 tumors with an apparently normal karyotype, and in 4 tumors with complex abnormalities without cytogenetically visible alterations of chromosomes 12. Rearrangements of HMGIY or its immediate surroundings were shown for 21 cases with 6p21 aberrations and three cases with other chromosomal abnormalities but without cytogenetically visible alterations of chromosomes 6. Genes Chromosomes Cancer 26:125-133, 1999.
Assuntos
Hamartoma/genética , Proteínas de Grupo de Alta Mobilidade/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Adolescente , Adulto , Idoso , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 6/genética , Proteína HMGA1a , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
The HMGIC gene, located in chromosome band 12q15, is rearranged in many different benign human tumors, often resulting in its fusion to ectopic sequences from other genes. The t(3;12)(q27;q14-q15) fuses HMGIC with the LPP gene and has so far been described exclusively in lipomas. Thus, it can be hypothesized that this particular gene fusion determines the adipocytic differentiation. We studied five pulmonary chondroid hamartomas all showing a t(3;12)(q27;q14-q15) that apparently was identical to the one observed in lipomas. By fluorescence in situ hybridization we found that both HMGIC and LPP are disrupted by this translocation. By RT-PCR the existence of a HMGIC/LPP fusion gene was confirmed. These results show that the fusion is not specific for lipomas. We favor the hypothesis that it is an ectopic sequence fused to HMGIC that is responsible for a cell shift to an embryogenic stage. Following this hypothesis the phenotype of the tumor may be induced by extracellular signal transduction.
Assuntos
Adipócitos/metabolismo , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 3/genética , Proteínas do Citoesqueleto , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Fusão Oncogênica/genética , Proteínas/genética , Translocação Genética/genética , Adipócitos/patologia , Clonagem Molecular , Proteína HMGA2 , Células HeLa , Humanos , Hibridização in Situ Fluorescente , Proteínas com Domínio LIM , Lipoma , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Células Tumorais CultivadasRESUMO
Recently, the high mobility group (HMG) proteins have attracted a lot of interest since it was shown that some members of that group can causally be involved in tumorigenesis. One HMG protein gene member is HMG1 for which the number of related DNA sequences has been estimated to be approximately 20-30. Nevertheless, besides the gene for HMG1 only one retropseudogene has been molecularly characterized. It was the aim of this study to map and characterize further sequences related to HMG1. PCR-screening of a PAC library resulted in 25 very strongly positive clones apparently containing HMG1-like cDNA sequences. Of eight clones which were further investigated five were distinguishable from each other based on their chromosome assignment and DNA sequence. Due to their homology to the HMG1 gene the DNA sequences were designated as HMG1L1, HMG1L3, HMG1L4, HMG1L5, and HMG1L6. By FISH experiments they were assigned to 2q32, 2q35, 3p24, 15q22, and 20q13, respectively. Except for one sequence, they did not show mutations leading to a frame shift or a new termination codon. Thus, we cannot exclude that these four HMG1-related DNA sequences represent active genes or can at least be activated e.g. by chromosome rearrangements in tumor cells. So far, the existence of six genes encoding HMG proteins has been described but because of a high frequency of closely related DNA sequences in the human genome it can be assumed that some of them are either pseudogenes or very similar genes.
