SRY mutation and tumor formation on the gonads of XY pure gonadal dysgenesis patients

We report three patients with XY pure gonadal dysgenesis. Two of these pati ents developed gonadoblastoma and associated dysgerminoma. Molecular analys es were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations, Deletion analyses were performe d by polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the Y chromosome that included the PABY, SRY. DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an ass ociated tumor. In the of her two patients who did not demonstrate such a de letion, the sequence of the SRY open reading frame was determined by the di deoxynucleotide method. Two nucleotide substitutions followed by a seven nu cleotide deletion were observed in the 3' end of HMG (high mobility group)- box in the other patient (15-years-old) with an associated tumor. The patie nt (22-years-old) without an associated tumor did not have the cryptic dele tion or mutation of SRY. A Y chromosome specific sequence (DYZ1) was demons trated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation o f gonadal tumors, especially dysgerminoma. (C) Elsevier Science Inc., 1999. All rights reserved.