TABLE 7.
Candidate tumor suppressors: LOH in human orthologs of GMR-dRetMEN2 enhancers
| Gene | GMR-dRetMEN2B | Human ortholog | Human location | Type of protein/ function | LOH pheos | LOH MTC |
|---|---|---|---|---|---|---|
| msn | E | NIK | 2q11.2–q12 | Ste20 serine/threonine kinase | 1/9 | 0/11 |
| MINK | 17p13.1 | Ste 20 serine/threonine kinase | 4/10 | ND | ||
| TNIK | 3q26.31 | Ste20 serine/threonine kinase | 86% (6/7) | 1/11 | ||
| dCsk | E | Csk | 15q23–25 | C-terminal Src kinase | 1/8 | 0/10 |
| hedgehog | E | shh | 7q36 | Hedgehog pathway ligand | 0/7 | 2/13 |
| indian hh | 2q33–q35 | Hedgehog pathway ligand | 1/7 | 0/13 | ||
| desert hh | 12q12–q13 | Hedgehog pathway ligand | 0/6 | 0/11 | ||
| Sin3A | E | DKFZP434K2235 | 15q23 | Part of SIN3 HDAC complexes | 0/11 | 0/7 |
| dMi-2 | E | CHD3 (Mi-2 alpha) | 17p13.1 | Part of the NuRD HDAC complex | 50% (3/6) | 0/11 |
| CHD4 (Mi-2 beta) | 12p13 | Part of the NuRD HDAC complex | 1/10 | 1/13 |
Human orthologs to select GMR-dRetMEN2 enhancers (E) were identified on the basis of sequence and functional similarity. Cytological map positions are listed for human orthologs. Both familial and sporadic pheochromocytoma (pheos) and MTCs were scanned for somatic deletions by LOH analysis using intragenic markers (see materials and methods and text for details). In some cases, patients were not heterozygous for the markers used and these cases were not informative and are excluded from the tallies listed. Underlining indicates loci with a high rate of LOH. Three of the four allelic losses observed in MTCs were in a single tumor. ND, not determined.