American Journal of Medical Genetics最新文献

The field of molecular cytogenetics has had a great impact on many aspects of medical and basic sciences. During the past 30 years, the application of molecular cytogenetic methodologies has resulted in remarkable advances in the field of cancer genetics and cytogenetics. These advances have led to the establishment of chromosome patterns as diagnostic and prognostic indexes in an array of acute and chronic leukemias and lymphomas, as key information in BMT, and as guides for the localization of oncogenes and tumor suppressor genes that are apparently responsible for the development of neoplastic states. With such information, the physician is in a more favorable position to devise therapy, appraise diagnosis, and plan follow-up.

Genetic alterations identified in human ovarian tumors by conventional banding, fluorescence in situ hybridization, comparative genomic hybridization, chromosome microdissection, loss of heterozygosity, chromosome microcell-mediated chromosome transfer, and microarray gene expression analysis are summarized and correlated. The significance of these findings with respect to pathologic classification and clinical application are discussed.

Leukemia is manifested in about 1-2% of people in Western industrialized nations. The most common form of leukemia is B-cell chronic lymphocytic leukemia (B-CLL), which accounts for approximately 30% of all cases. While CLL's etiology remains elusive, there is increasing evidence that substantially supports the role of hereditary factors in a subset of cases of this disease. Our purpose is to describe an extremely well documented CLL family wherein the disease has been verified in a father and his four sons; two of the sons are identical twins. The family history, including available medical records and pathology reports, was gathered and reviewed. Peripheral blood lymphocytes were used for cytogenetic and fluorescence in situ hybridization analyses. The family reported herein shows classic findings in support of an autosomal dominant mode of genetic transmission of CLL. Given the explosive developments in molecular genetics during the past decade, it is certain that families of this type will provide important clues to the etiology, pathogenesis, and ultimate prevention of CLL.

Chromosomal abnormalities have been implicated in cancer development since the turn of the last century. Only during the past two decades, with advances in cytogenetics and molecular biology, has the genetic basis of neoplasia been firmly established, however, with chromosomal alterations being recognized as critical in the pathogenesis of human cancer. Recurrent chromosomal alterations provide cytological and molecular markers for the diagnosis and prognosis of disease. They also facilitate the identification of genes that are important in carcinogenesis and, ultimately, may lead to the development of targeted therapy. In breast cancer, the most prevalent malignancy among females, substantial progress has been achieved in identifying genes located at sites of recurrent chromosomal alterations and in profiling gene expression through the application of powerful cytogenetic and functional genomic techniques. Characterization of the molecular pathologic characteristics and gene-expression profiles of breast cancer should provide new clinical tools for the accurate diagnosis and prediction of prognosis as well as new targets for the development of therapeutic agents.

There exist numerous genetic disorders, marked by chromosome instability, that are strikingly associated with various cancers. Both the chromosomal instabilities and neoplastic outcomes are related to abnormalities of DNA metabolism, DNA repair, cell-cycle governance, or control of apoptosis. Among these diseases are ataxia telangectasia and Nijmegen breakage syndrome, with increased incidences of lymphomas. Bloom syndrome, Werner syndrome, and Rothmund-Thompson syndrome, each characterized by a DNA helicase defect, are associated with early incidences of different cancers. Other diseases combining the phenotype of chromosomal instabilities and neoplastic development are Fanconi anemia and breast cancers associated with mutant BRCA1 and BRCA2 genes. The cloning of the encoding genes and the characterization of their products have resulted in partial understanding of the pathways of cellular DNA surveillance and maintenance of genomic rectitude. The exact pathways fully linking the genetic defect mechanisms to the eventual development of various neoplasias remain to be elucidated, but progress in defining the molecular genetics of these entities suggests that many of them are disorders of DNA recombination. Each defect involves a separate protein in these complex pathways.

Various types of cytogenetic and molecular cytogenetic approaches, including conventional banding, fluorescence in situ hybridization (FISH), fiber-FISH, comparative genomic hybridization (CGH), matrix array CGH, chromosome microdissection, and microcell-mediated chromosome transfer are summarized. The rationale, advantage, and limitations of each approach are discussed with respect to research and clinical applications in human neoplasia.

Prostate cancer remains the most common male malignancy in Western countries and the second-leading cause of death from cancer in males. Progress in the understanding of molecular and genetic mechanisms leading to this disease has only recently begun to offer a glimpse of the genes, chromosomal sites, and proteins implicated in the development and progression of prostate tumors. This brief review addresses some of the key issues in prostate cancer research, including a discussion of both hereditary and sporadic cancers as well as specific genes and chromosomal loci that likely play a part in the etiology of this disease.