CHROMOSOME MUTATION IN THE PATHOGENESIS OF AIDS

获得性免疫缺陷综合征/卡波西肉瘤(AIDS/KS) 一个新承认的临床实体，但受影响的人构成 最近发现的癌症易发人群。细胞遗传学研究 癌症易发人群几乎总是具有启发性，而这样的 这里建议对艾滋病/KS人群进行研究。我们的决定 进行这项研究与我们对另一项的长期研究是一致的 癌症易患人群，即那些从基因上决定 罹患“染色体断裂综合症”之一的癌症。我们的 引起了人们对这项研究的兴趣，特别是因为有一个特征 在艾滋病/KS和两种遗传综合征中都很突出， 共济失调-毛细血管扩张(AT)和布卢姆综合征-严重的免疫缺陷。 在调查的初始阶段，对来自 艾滋病/KS人群中的人将使用常规 我们实验室日常使用的细胞遗传学技术。要确定 受影响的人是否提出证据表明对 它们体细胞的遗传物质已经或正在发生， 它们细胞中染色单体断裂、间隙和重排以及 姐妹染色单体交换的频率将与患有 AT、BS和相关疾病(这些数据已经在我们的文件中)和 在对照组中，包括健康的男性同性恋人口。至 确定受影响的人是否携带有淋巴细胞克隆 突变的染色体补体在他们的循环或淋巴结中， 将对G显带的早中期染色体标本进行稳定性检查 染色体重排。(这种克隆很容易在AT、 艾滋病患者在许多方面都相似的情况，而且在 暴露于电离辐射和致癌的人的比例 化学品。)检测到的克隆将被连续跟踪，例如每隔 两树月，以确定它们的进化，可能包括进化 变成了一个临床上可以识别为癌症的克隆。(一种战略 使用所有真正的患者的冷冻淋巴细胞样本将是 受雇，这将使这种长期研究得以追溯 少数人实际上会患上癌症；也是细胞遗传学的 将对培养的细胞进行分析，包括自发发育 淋巴母细胞系。

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.