Evidence for telomeric fusions as a mechanism for recurring structural aberrations of chromosome 11 in giant cell tumor of bone

Abstract Giant cell tumor of bone (GCTB) is a benign but often aggressive tumor with a tendency toward local recurrence. Telomeric associations (tas) or telomeric fusions are common cytogenetic findings that have been implicated in the initiation of chromosome instability and tumorigenesis. We performed cytogenetic studies on 5 cases of GCTB to further characterize chromosome aberrations in these tumors. Four of the 5 cases showed abnormal karyotypes with clonal telomeric fusions involving chromosome 11. In 3 cases, the telomeric fusions of 11pter were apparently the precursor lesions to the progression of sub-clones with structural chromosome aberrations of 11p. Two tumors demonstrated a similar pattern of progression resulting in whole arm losses of 11p, including sub-clones with both whole-arm unbalanced translocations and whole-arm deletions. A third tumor with clonal tas of 11pter showed 2 additional subclones, one with ring chromosome 11 and the other with an extra copy of 1q. To our knowledge, the 2 cases with del(11)(p11) represent the first report of a recurring structural chromosome aberration in GCTB. These findings support the concept that telomeric instability is responsible for a large degree of intratumor heterogeneity and serves as a precursor lesion to subsequent clonal structural aberrations of chromosome 11 in GCTB.