Correspondence

Germ-Line Mutations of the p53 Tumor-Suppressor Gene in Children and Young Adults with Second Malignant Neoplasms

N Engl J Med 1997; 336:734March 6, 1997

Article

To the Editor:

In our article on germ-line mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms (May 14, 1992, issue),1 we reported that the proband (II-1) and her mother (I-2) in Family 6 carried germ-line point mutations in the p53 gene that resulted in an amino acid change from arginine to tryptophan at codon 248 (Figure 1 and Figure 3). The proband's father and sister were reported to carry wild-type p53. As part of a clinical program of genetic testing, a second p53 analysis was performed on a new blood specimen from the proband, and no mutations were found. Remnants of the proband's original DNA sample and new samples from other unaffected family members also showed normal p53 genes. No DNA remained from the deceased mother. We have reexamined samples from the other three families (Families 15, 38, and 49) and have found the mutations to be as we described in our paper. Although we have not been able to confirm the cause of the error with regard to Family 6, possible explanations include a mix-up of the specimens or contamination with polymerase-chain-reaction products containing mutations at codon 248. This experience calls attention to the possibility of false positive results in genetic testing, which can be harmful if they are used in decisions affecting clinical management.

The occurrence of germ-line p53 mutations in the other families, as well as in subsequent reports in the literature, indicates that the scientific message of the original work — that germ-line p53 mutations can be found in young patients affected with multiple second neoplasms — remains intact.

David Malkin, M.D.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

Stephen H. Friend, M.D., Ph.D.
Fred Hutchinson Cancer Research Center, 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

1 References

1. 1

   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
   Full Text | Web of Science | Medline

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   Anna Patrikidou, Jon Bennett, Patrick Abou-Sleiman, Joy D.A. Delhanty, Malcolm Harris. (2002) A novel, de novo germline TP53 mutation in a rare presentation of the Li-Fraumeni syndrome in the maxilla. Oral Oncology 38:4, 383-390
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   John Moppett, Anthony Oakhill, Andrew W. Duncan. (2001) Second malignancies in children: the usual suspects?. European Journal of Radiology 38:3, 235-248
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