A tumor suppressor locus in familial and sporadic chordoma maps to 1p36

Previous cytogenetic/FISH data have demonstrated Ip36 deletions in a relaps ing familial clivus chordoma developed by a patient who has 2 daughters, re spectively affected with childhood astrocytoma and clivus chordoma. Using a n approach that combined the LOH (loss of heterozygosity) study of the fath er chordoma and the daughter astrocytoma and a segregation analysis from pa rents Co sibs using 17 CA-repeats spanning Ip36.32-Ip36.11, we mapped the c ancer susceptibility locus in this family to the Ip36 region. The LOH and h aplotype information was elaborated using a pairwise linkage analysis that gave a maximum lod score of 1.2. Additional LOH data relating to 6 sporadic chordomas allowed us to define an SRO (the smallest region of overlapping loss) of about 25 cM from DIS2845 (1p36.31) to DIS2728 (Ip36.13). Our overa ll findings converge on mapping to Ip36 a tumor-suppressor gene involved in familial and sporadic chordoma. Int. J. Cancer 87:68-72, 2000. (C) 2000 Wi ley-Liss, Inc.