Cytogenetics and genetics of human cancer: methods and accomplishments.

Cytogenetic and related changes in human cancer constitute part of a constantly developing and enlarging continuum of known genetic alterations associated with cancer development and biology. The cytogenetic component of this continuum has fulfilled much of its pioneering role and now constitutes a small but dynamic segment of the vast literature on cancer genetics, in which it has played an important if not initiating role. The goals of this article are (a) to address historical and methodological aspects of cancer cytogenetics; (b) to present information on diagnostic translocations in leukemias, lymphomas, bone and soft tissue tumors, and carcinomas; (c) to connect some of these chromosomal aberrations with their molecular equivalents; and (d) to describe anomalies in some solid tumors indicative of the complexity of the genomic alterations in cancer. We also look at a few of the more recent genomic developments in cancer and offer an opinion as to what all these findings add up to.

Genetics of chondrosarcoma and related tumors.

PURPOSE OF REVIEW: The burgeoning body of information on the genetic changes present in and underlying the development and biology of human cancers has carried implications regarding the possible genetic events that are responsible for not only the genesis of these cancers but also the hope of the cure for these cancers. Chondrosarcomas are a group of tumors that fall into this category. The purpose of this review is to summarize the genetic findings in these tumors. RECENT FINDINGS: The histopathologic variability of chondrosarcomas is reflected in the complexity and lack of specificity of their cytogenetic and molecular genetic findings, except for extraskeletal myxoid chondrosarcomas. These are characterized in the preponderant number of cases by a translocation, t(9;22)(q22;q12), and in a small number of cases by variant translocations t(9;17)(q22;q11) and t(9;15)(q22;q21). These translocations lead to the formation of abnormal fusion genes and gene products (proteins). In each of these translocations, the CHN gene is involved, resulting in the chimeric fusion genes EWS/CHN, RBP56/CHN, and TCF12/CHN, respectively. The specific translocations and their associated molecular genetic changes are diagnostic of extraskeletal myxoid chondrosarcomas. The abnormal proteins resulting from these fusion genes aberrantly affect gene transcription and cellular signaling pathways thought to be responsible for initiating sarcoma formation. In skeletal (central) chondrosarcomas of varying histopathologic types, the cytogenetic and molecular genetic findings are variable, complex, and apparently lacking in specificity. These changes may reflect a stepwise process (or processes) of oncogenesis involving an array of genes. SUMMARY: Although some cartilaginous tumors are characterized by specific or recurrent chromosome alterations and molecular genetic changes, much is yet to be learned about the nature and sequence of these genetics events and about their unique role in the stepwise process involved in the development and biology of each tumor type, both malignant and nonmalignant. Until such time, some of the genetic changes, particularly the presence of specific translocations, can be of definite diagnostic value.

Dermatofibrosarcoma protuberans of breast.

We describe the case of a 57-year-old woman with a tumor of the breast suspected of being a dermatofibrosarcoma protuberans (DFSP). To confirm the diagnosis, molecular studies were performed on fixed tumor and revealed the presence of the fusion product of the COL1A1-PDGFB genes characteristic of DFSP.

Molecular cytogenetic aspects of hematological malignancies: clinical implications.

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.

Cytogenetics and molecular genetics of bladder cancer: a personal view.

The cytogenetic and molecular genetic aspects that may be involved in the pathogenesis of bladder cancer are presented. Although anomalies of chromosome 9 may play an initial causative role in this cancer, the subsequent events, involving a succession of genetic changes, are less established or understood. This presentation is a distillation of what generally are considered to be the cytogenetic and molecular genetic events that constitute the array of changes underlying bladder cancer.

Cytogenetics and molecular genetics of bone and soft-tissue tumors.

The cytogenetic and molecular findings in bone and soft-tissue sarcomas are summarized. A table presenting all such tumors, with their specific translocations and the genes involved, is included, along with a list of those tumors that most likely result from a stepwise process of numerous genetic changes.