HIF1α expression is lost in many VHL–/– renal carcinoma
lines, can suppress tumor formation by VHL–/– renal carcinoma
cells when overexpressed, and maps to 14q23. In
contrast, previous studies, including our own, pinpointed
14q31-ter as the most likely region to harbor a kidney cancer
tumor suppressor gene. Nonetheless, the 14q
deletions in kidney cancer are typically very large, with the localization
to 14q31-ter based on relatively rare kidney cancers
with smaller deletions. For example, in our recent analysis of
90 clear cell renal carcinomas, 39 tumors (43%) had sustained
14q deletions . Of these, 36 (93%) were large deletions
that also encompassed the HIF1α locus . This observation
suggests the existence of multiple tumor suppressor
genes on 14q, including, perhaps, HIF1α. Consistent with
this hypothesis, deletions affecting HIF1α are more common
in kidney cancer than in the other 16 tumor types for which
we have ≥40 samples (Fig. 1D). This strong bias toward kidney
cancer is not apparent, however, if one includes deletions
elsewhere on 14q (Supplementary Fig. S1).