CLUSTERED MUTATIONS IN THE 2ND EXON OF THE MYC GENE IN SPORADIC BURKITT-LYMPHOMA

The primary tumors from 15 untreated patients with Burkitt's lymphoma were analysed for abnormalities in the coding region of the MYC gene b y single stranded conformational polymorphism (SSCP) analysis followed by DNA sequencing. Fourteen of the 15 tumors had one or more clonal m utations. Forty one mutations were found in the second exon; only one occurred in the third exon. Seven tumors had mutations that clustered in a region spanning amino acids 38-63. Four of these possessed mutati ons that altered prolines at positions 57 (3), 60 (1), and 63 (1). Sev en tumors were mutated in the central portions of the second exon. The se occurred at position 95 (2), position 115 (2), position 137 (1), an d position 138 (3). Analysis of the published sequences from five lymp homa cell lines and one primary tumor showed a similar clustering of m utations, with all six having mutations in codons between positions 38 -63. The regions where mutations occurred have been associated with a variety of properties, including transcriptional activation and cellul ar transformation. The number and location of mutations showed no corr elation with either chromosome 8 or chromosome 14 breakpoints or with the Epstein-Bar virus positivity of the tumors. This unexpected, frequ ent occurrence of clustered mutations in the second exon of the MYC ge ne suggests a rote for the mutated MYC proteins in the pathogenesis of Burkitt's lymphoma, possibly through altered interactions of this dom ain with other cellular factors.