A familial cancer aggregation comprising sarcomas, brain tumors, leukemias, and carcinomas of breast, larynx, lung, adrenal cortex, and other sites has been studied from a pathologic-genetic standpoint. Based upon sibships segregating for cancer, the genetic segregation parameter is estimated to be 45.6 f 11% which is compatible with that expected for a rare deleterious autosomal gene showing complete dominance. Pathologic review of 16 tumors by bright field microscopy revealed variable occurrences of intranuclear cytoplasmic in-vaginations, intranucleolar bodies, and acidophilic intracytoplasmic inclusions in eight lesions. Two tumors showed both intranuclear cytoplasmic in-vaginations and intranucleolar inclusions. Morphological findings coupled with the observed pattern and distribution of cancer in the subject kindred suggest that the cancer-prone genotype interacts with one or more exogenous factors in causing this familial tumor association.

Breast cancer risk factors are closely intertwined with the patient's cultural background, which may contribute to breast cancer aggregations within families. The difficult questions are: (1) does a truly hereditary breast cancer subset exist; (2) which familial aggregations are hereditary; and (3) is the hereditary form distinctive from its sporadic counterpart? These queries will be resolved once biomarkers are identified that show high sensitivity and specificity with genotype. The authors provide a review of this subject and will focus on their recent discovery of increased in vitro hyperdiploidy in cultured skin fibroblasts from patients with or at risk for hereditary breast cancer. The authors discuss findings from their study of family histories in 225 consecutively ascertained patients with verified breast cancer from the Creighton University School of Medicine Oncology Clinic. Findings consistent with an hereditary breast cancer syndrome were identified in 5% of the patients. Given the 112,000 new cases of breast cancer in the United States in 1982, the authors estimate that with a confidence coefficient of 0.95 between 2410 and 8790 of these individuals will manifest hereditary breast cancer. Specific surveillance/management programs should be geared to high‐risk members of these families in which cancer yield will be predictable.

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IS6110-Based PCR Methods for Detection of Mycobacterium tuberculosis Kent et al. (3) detected Mycobacterium tuberculosis by a nested PCR test that amplified a 181-bp target located in insertion sequence IS6110, but they also encountered many false-positive results when the test was applied to isolates of mycobacteria that do not belong to the M. tuberculosis complex. Because the investigators attributed the false positives to homology between IS6110 and genomic DNA of the other mycobacterial species, they warned that false-positive PCR results could be a problem with some IS6110-based methods for detection of M. tuberculosis complex. Our recent experience in using IS6110-based amplifications for detection of M. tuberculosis complex is informative on this issue. We selected two such amplifications that others had developed, with respective 123-bp (2) and 317-bp (1, 4) targets, and after slightly modifying the procedures incorporated them into a dual-PCR clinical protocol that we applied to mycobacterial colonies grown on Löwenstein-Jensen or Middlebrook 7H11 medium. The modifications that we made included use of dUTP (rather than dTTP) in both reaction mixes and use of a cycling program that was the same for both amplfications (30 cycles; cycle 1: 94ЊC for 5 min, 68ЊC for 45 s, 72ЊC for 90 s; cycles 2 through 30: 94ЊC for 45 s, 68ЊC for 45 s, 72ЊC for 90 s). The two amplifications were performed in separate tubes in a single thermal-cycler run, and the two amplified products were then electrophoresed in separate lanes of the same ethidium bromide-stained 2% agarose gel. In initial validation studies and in subsequent routine clinical examinations, we used this dual-PCR procedure in blindly testing 116 mycobacterial isolates, all of which were also identified to the species (or complex) level by the Mycobacteriology Laboratory of the New Jersey State Department of Health on the basis of their colony characteristics, chemical reactions, patterns shown on highpressure liquid chromatography, and DNA-rRNA hybridizations. The results produced by the dual-PCR procedure and the final identifications by the state laboratory were in total agreement for all 116 isolates: they were positive for M. tuberculosis complex in 46 cases and negative in the remaining 70. Identifications made by the state laboratory on the 70 isolates negative for M. tuberculosis complex were as follows: M. avium-M. intracellulare complex, 50; M. xenopi, 7; M. gordonae, 7; M. fortuitum, 5; and M. kansasii, 1. (In the entire series of 116 cultures, there was a single specimen for which the initial PCR results were discrepant, i.e., the 123-bp target was amplified but the 317-bp target was not. An advantage of the dual-PCR approach was demonstrated in th is case, in that duplicate repeats with the two sets of applicable primer pairs produced amplification of both targets, thus identifying the culture as positive for M. tuberculosis complex. This diagnosis was later confirmed by the state laboratory.) Kent et al.'s call for careful validation of any IS61...

A medical genetic study has been undertaken of a large segment of an inbred Dutch kindred containing more than 2000 members. Noteworthy are occurrences of several hereditary precancerous diseases among the family members. These include two siblings with xeroderma pigmentosum and two siblings from another sibship who manifest a syndrome which may possibly be a variant of Fanconi's aplastic anemia. Four patients had histologically verified testicular malignant neoplasms. Other generally rarely occurring cancers included Wilms' tumor, thymic carcinoma, and astrocytoma. At present there is no satisfactory etiologic explanation for these events in this family. Environmental factors common to the family cannot be excluded. Hereditary factors conditioned strongly by consanguinity may be operating in concert with as yet unknown non‐genetic factors such as an oncogenic virus.