Table 1.
Study Participants with Confirmed Somatic Mutations in or Linked to the Shh Pathway
| Subject |
Genomic Analysis Method(s) |
Annotation of Candidate Mutations | Shh Gene(s) (KEGG) | VAF Brain | VAF Blood | Method of Detection | ||
|---|---|---|---|---|---|---|---|---|
| WES | CMA | TRS | ||||||
| hht25086 | × | − | − | c.984dupT (p.Asp329Ter) [GenBank: NM_002730.3] | PRKACA | 25% | 0.5% | WES, confirmed by Sanger |
| hht238a | × | − | − | c.983_984delTT (p.Phe328Ter) [GenBank: NM_002730.3] | PRKACA | 23% | 0% | WES, confirmed by Sanger |
| hht1198c | × | × | − | chr7q LOH (chr7:58,814,064–159,138,663) | SHH, SMO, WNT16, WNT2 | NA | NA | WES, confirmed by CMA |
| hht735 | × | × | × | chr16p LOH (chr16:0–31,543,619) | CREBBPa | NA | NA | WES, confirmed by CMA |
| hht209 | × | − | − | c.2989dupG (p.Ala997GlyfsTer87) [GenBank: NM_000168.5] | GLI3 | 57% | 0% | WES, confirmed by Sanger |
| hht26139 | × | − | − | c.3442C>T (p.Gln1148Ter) [GenBank: NM_000168.5] | GLI3 | 24% | 0% | WES, confirmed by Sanger |
| hht880 | − | × | − | chr2q12.1–q37.3 LOH (chr2:103,856,408–243,199,373) | GLI2, IHH, LRP2, STK36, WNT10A, WNT6 | NA | NA | CMA |
| hht953 | − | × | − | chr14q11.2–q32.33 LOH (chr14:24,419,118–106,072,470) | BMP4, AKT1 | NA | NA | CMA |
| hht25057 | − | × | − | chr16p11.2–p13.3 LOH (chr16:0–31543619) | CREBBPa | NA | NA | CMA |
| hht25063 | − | × | − | chr7p22.1–q36.3 CNG, CNL (chr7:986211–60069242, 58814064–159138663) | GLI3, SHH, SMO, WNT16, WNT2 | NA | NA | CMA |
| hht25094 | − | × | − | chr11q12.3–q25 LOH (chr11:64879188–135006516) | WNT11 | NA | NA | CMA |
| hht25077 | − | × | × | c.3172C>T (p.Arg1058Ter) [GenBank: NM_000168.5] | GLI3 | 18% | 0% | TRS, confirmed by Sanger |
| hht31536 | − | × | × | c.2071C>T (p.Gln691Ter) [GenBank: NM_000168.5] | GLI3 | 37% | 0.8% | TRS, confirmed by Sanger |
| hht25085 | − | − | − | c.226-231dup (p.Asp76_Lys77dup) [GenBank: NM_002730.3] | PRKACAb | – | – | Sanger |
Shh, sonic hedgehog; VAF, variant allele frequency; LOH, loss of heterozygosity (might be copy-number neutral LOH); CNG, copy-number gain; CNL, copy-number loss; WES, whole-exome sequencing; CMA, chromosomal microarray; TRS, targeted resequencing; ×, used; −, not used; NA, not applicable. All coordinates correspond to the UCSC Genome Browser reference genome (GRCH37/hg19).
a
Transcriptional regulator of the Shh pathway.
b
Identified by Sanger sequencing.