Not only is acquired immunodeficiency syndrome / Kaposi's sarcoma (AIDS/KS) a newly recognized clinical entity, but the persons affected constitute the most recently recognized cancer-prone population. Cytogenetic studies of cancer-prone populations almost always have been illuminating, and such a study is proposed here in the case of the AIDS/KS population. Our decision to undertake this study is consonant with our long-term study of another cancer-prone population, namely, those persons genetically determined to develop cancer who have one of the """"""""chromosome-breakage syndromes."""""""" Our interest in the study was engendered especially because of one feature that is prominent in both AIDS/KS and two of the genetic syndromes, ataxia-telangiectasia (AT) and Bloom's syndrome--severe immune deficiency. During the initial phase of the investigation, analyses of cells from persons in the AIDS/KS population will be made using conventional cytogenetic techniques in daily use in our laboratory. To determine whether affected persons present evidence that excessive damage to the genetic material of their somatic cells has occurred, or is occurring, the frequency in their cells of chromatid breaks, gaps, and rearrangements and of sister-chromatid exchanges will be compared with that in persons with AT, BS, and related disorders (these data are in our files already) and that in controls, including a healthy male homosexual population. To determine whether affected persons harbor clones of lymphocytes with mutated chromosome complements in their circulation or lymph nodes, G-banded prometaphase chromosome preparations will be examined for stable chromosome rearrangements. (Such clones are found readily in AT, the condition which in many respects the AIDS patients resemble, and also in a proportion of persons exposed to ionizing radiation and carcinogenic chemicals.) Clones detected will be followed serially, e.g., every two-tree months, to determine their evolution, possibly including evolution into a clone that would be clinically recognizable as cancer. (A strategy using frozen lymphocyte samples from all bona fide patients will be employed that will permit such long-term studies to be made retrospectively in the minority that actually will develop cancer; also cytogenetic analysis will be made of cultured cells, including spontaneously-developing lymphoblastoid cell lines.
| German, James; Sanz, Maureen M; Ciocci, Susan et al. (2007) Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. Hum Mutat 28:743-53 |
