Monograph on Li-Fraumeni syndrome written by Dr. David Malkin and edited by Arnold Levine: In 1969, Li and Fraumeni described a notable cancer predisposition syndrome. Using a classic epidemiological approach, they conducted a retrospective review of 280 medical charts and 418 death certificates of children diagnosed with rhabdomyosarcoma in the U.S. between 1960 and 1964. Five families were identified in which a second child had developed a soft tissue sarcoma. They also observed a high frequency of various cancer types among first- and second-degree adult relatives along a single ancestral lineage, with cancer rates significantly higher than expected by chance alone. In addition to soft tissue sarcomas and premenopausal breast cancers, other cancers such as lung, skin, pancreas or adrenal cortex carcinomas, leukemia, and various brain tumors were noted. Several family members also developed multiple metachronous primary neoplasms. Li and Fraumeni proposed that the diverse cancers within these families might reflect the tendency for an individual to develop multiple primary tumors, and suggested that these families could represent a previously unrecognized familial cancer syndrome, likely inherited in an autosomal dominant manner.
