To the Editor: In our article on germ-line mutations of thep53 tumor-suppressor gene in children and young adults withsecond malignant neoplasms (May 14, 1992, issue),1 we reportedthat the proband (II-1) and her mother (I-2) in Family 6 carriedgerm-line point mutations in the p53 gene that resulted in anamino acid change from arginine to tryptophan at codon 248 (Figure1 and Figure 3). The proband's father and sister were reportedto carry wild-type p53. As part of a clinical program of genetictesting, a second p53 analysis was performed on a new bloodspecimen from the proband, and no mutations were found. Remnantsof the proband's original DNA sample and new samples from otherunaffected family members also showed normal p53 genes. No DNAremained from the deceased mother. We have reexamined samplesfrom the other three families (Families 15, 38, and 49) andhave found the mutations to be as we described in our paper.Although we have not been able to confirm the cause of the errorwith regard to Family 6, possible explanations include a mix-upof the specimens or contamination with polymerase-chain-reactionproducts containing mutations at codon 248. This experiencecalls attention to the possibility of false positive resultsin genetic testing, which can be harmful if they are used indecisions affecting clinical management.
The occurrence of germ-line p53 mutations in the other families,as well as in subsequent reports in the literature, indicatesthat the scientific message of the original work — thatgerm-line p53 mutations can be found in young patients affectedwith multiple second neoplasms — remains intact.
David Malkin, M.D. Hospital for Sick Children Toronto, ON M5G1X8, Canada
Stephen H. Friend, M.D., Ph.D. Fred Hutchinson Cancer ResearchCenter Seattle, WA 98104
Frederick P. Li, M.D. Dana–Farber Cancer Institute Boston,MA 02115
Louise C. Strong, M.D., Ph.D. M.D. Anderson Cancer Center Houston,TX 77030
References
Malkin D, Jolly KW, Barbier N, et al. Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med 1992;326:1309-1315. [Abstract]
Evans, D G R, Birch, J M, Thorneycroft, M, McGown, G, Lalloo, F, Varley, J M
(2002). Low rate of TP53 germline mutations in breast cancer/sarcoma families not fulfilling classical criteria for Li-Fraumeni syndrome. J. Med. Genet.
39: 941-944
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