Table 2. Sequence Results from Children with DICER1 Mosaic RNase IIIb Mutations.
| Study ID | Tissue source | Tumor
purity a |
RNase IIIb domain
hotspot mutation |
Hotspot allele freq.
b
(variant/total reads) |
Loss of function mutation | LOF allele freq.
b
(variant/total reads) |
|---|---|---|---|---|---|---|
| 101 | Blood | – | c.5126A>G; p.D1709G | Sanger c (NR) | ND | – |
| Normal lymph node | – | “ | 15.2% (10/66) | ND | – | |
| 102 | Blood | – | c.5125G>A; p.D1709N | 4.61% (22/477) | ND | – |
| Brain, PPB metastasis | 30% | “ | 51.0% (213/418) | Allele loss | – | |
| 103 | Blood | – | c.5125G>A; p.D1709N | 0.28% (18/6413) | ND | – |
| Kidney, CN | 40% | “ | 14.9% (174/1172) | c.1129G>A; p.V377I | 3.1% (5/159) | |
| Lung, PPB Type IR | 20% | “ | 16.2% (30/185) | c.1200G>A; p.W400* | 4.1% (11/141) | |
| Small intestine, polyp | 25% | “ | 17.5% (65/371) | c.96G>A; p.W32* | 3% (13/431) | |
| 104 | Blood | – | c.5428G>T; p.D1810Y | 0.21% (13/6217) | ND | – |
| Normal fallopian tube | – | “ | 7.19% (141/1961) | ND | – | |
| Lung, PPB Type IR | 20% | “ | 27.8% (193/694) | ND | – | |
| Kidney, CN | 20% | “ | 29.2% (64/219) | c.1711delT; p.S571Vfs*16 | 21.8% (73/192) | |
| Ovary (right), SLCT | 34% | “ | 34.2% (684/1988) | c.1775delA; p.K592Mfs*15 | 36.2% (721/1993) | |
| Ovary (left), SLCT | 95% | “ | 92.4% (1837/1988) | Allele loss | – | |
| 105 | Blood | – | c.5437G>C; p.E1813Q | 0.04% (1/2450) d | ND | – |
| Nasal cavity, NCMH | 20% | “ | 29.3% (579/1977) | ND | – | |
| Thyroid, follicular Ca | 60% | “ | 66.6% (289/434) | Allele loss | – | |
| Ovary (right), SLCT | 75% | “ | 76.8% (750/976) | Allele loss | – | |
| Ovary (left), SLCT | 25% | “ | 31.8% (624/1962) | c.4626delC; p.Q1542Hfs*18 | 21.7% (430/1984) | |
| 120
(de Kock 45 case 4) e |
Blood | – | ND | – | ND | – |
| Reactive lung | – | c.5425G>A; p.G1809R | 1% (36/3442) | ND | – | |
| Lung, PPB
type II |
NR | “ | 37% (1455/3972) | c.1966C>T; p.R656* | NR | |
| 123 | Blood | – | ND | – | ND | – |
| Normal ureter | – | c.5113G>A; p.E1705K | 13% (19/148) | ND | – | |
| Lung, PPB
type I |
20 | “ | 24% (46/192) | Allele loss | – | |
| Kidney, CN | 25 | “ | 35% (33/94) | Allele loss | – | |
| Klein
46
case 1 |
Blood | – | c.5138A>T; p.D1713V | 21% (NR) | ND | – |
| Normal kidney | – | “ | 35% (NR) | ND | – | |
| Wilms tumor | NR | “ | 37% (NR) | c.1304C>T; p.P453L | variable | |
| Klein
46
case 2 |
Blood | – | c.5125G>T; p.D1709Y | 28% (NR) | ND | – |
| Normal kidney | – | “ | 35% (NR) | ND | – | |
| Wilms tumor | NR | “ | 47% (NR) | ND | – | |
| De Kock
11
case 12 |
Blood | – | c.5125G>C; p.D1709H | Sanger c (NR) | ND | – |
| Pituitary blastoma | NR | “ | Sanger c (NR) | Allele loss | – |
Abbreviations: Ca carcinoma; CN cystic nephroma; LOF loss of function; NCMH nasal chondromesenchymal hamartoma; ND none detected; NR not reported; PPB pleuropulmonary blastoma; SLCT Sertoli-Leydig cell tumor.
a. Percent tumor cells in specimen, estimated visually by microscopy in tumor sections.
b. Allele frequency estimates were derived from NGS read counts in this study. In the two cases reported by Klein et al., allele frequencies were determined by pyrosequencing assays.
c. Hotspot allele detected by Sanger sequencing only; no NGS performed.
d. Variant allele frequency below estimated error rate for base substitutions (0.07%) with Ion Torrent using 200 bp sequencing kit 47.
e. Note addded in revision: Sequence data shown for study ID# 120 was published by de Kock et al. 45. We concur in their conclusion of mosaicism.