Table 3.
Tumor characteristics and targeted exome sequencing results in ACC.
| Tumor Number | NICD1 Staining Pattern | Tumor Location / Type | Growth Pattern | NOTCH1 Mutations | Additional Mutations / Aberrations (Affected gene or chromosomal region) |
|---|---|---|---|---|---|
| 1 | Diffuse | Lung (metastasis) | Tubular/cribriform | None | PTEN |
| 2 | Diffuse | Thyroid (primary) | Solid | NOTCH1 c.7507C>T (p.Q2503*), exon 34 - in 57% of 38 reads | PIK3CA |
| 3 | Diffuse | Parotid gland (primary) | Solid | NOTCH1 c.7400_7400C>GTC (p.S2467fs), exon 34 - in 24% of 41 reads | PIK3CA |
| 4 | Diffuse | Trachea (primary) | Solid | NOTCH1 c.4744_4747CCGG>G (p.P1582del), exon 26 - in 36% of 131 reads | None |
| 5 | Diffuse | Trachea (primary) | Solid | NOTCH1 c.5162T>G (p.V1721G), exon 27 - in 38% of 113 reads; NOTCH1 c.7400C>A (p.S2467*), exon 34 - in 45% of 57 reads | None |
| 6 | Diffuse | Oropharynx | Solid | None | None |
| 7–9 | Diffuse (x3) | Trachea x 3 (primary + 2 recurrences) | Solid (x3) | One copy loss of NOTCH1 exons 1–27 (x3) | 6q loss except MYB exons 1-15 |
| 10 | Diffuse | Maxillary sinus (primary) | Solid | NOTCH1 c.4631A>C (p.H1544P), exon 26 - in 60% of 81 reads; NOTCH1 c7398_7399GT>T (p.2466fs), exon 34 – in 55% of 58 reads | ARID1A, CREBBP, 6q abnormality involving MYB |
| 11 | Diffuse | Liver (metastasis) | Solid | NOTCH1 c.4680C>A (p.D1560E), exon 26 - in 57% of 49 reads | ARID1A, KDM6A |
| 12 | Diffuse | Nasopharynx (primary) | Solid | None | None |
| 13-14 | Diffuse (x2) | Trachea (primary) + liver (metastasis) | Solid (x2) | NOTCH1 exon 27 duplication (primary), NOTCH1 exon 28 duplication (liver metastasis) | ARID1A (trachea); PMS2 (both biopsies) |
| 15 | Subset | Maxillary sinus (recurrence) | Tubular/cribriform | None | Low copy number gain of 9q34.3 |
| 16 | Subset (focally diffuse) | Submandibular gland (primary) | Tubular/cribriform and solid (focal) | None | Single copy number loss of 9q34.3 |
| 17 | Subset | Maxillary sinus, orbit (recurrence) | Tubular/cribriform | None | Numerous copy number changes |
| 18 | Subset | Submandibular gland (primary) | Tubular/cribriform | None | None |
| 19 | Subset | Pleura (metastasis) | Tubular/cribriform | None | None |
| 20 | Subset | Palate (primary) | Tubular/cribriform | None | NFIB-MYB fusion |
| 21 | Subset | Lung (metastasis) | Tubular/cribriform | None | Numerous copy number variants |
| 22 | Subset | Lung (metastasis) | Tubular/cribriform | None | MYB-NFIB fusion; del 22q11.21 |
| 23 | Subset | Liver (metastasis) | Tubular/cribriform | None | CREBP c.4557C>A (p.Y1519*), exon 27 - in 19% of 296 reads; low copy number gain of 9q34.3 and 6q23.3 (MYB) |
| 24 | Subset | Parotid (primary) | Tubular/cribriform | None | TP53, numerous copy number variants |
| 25 | Subset | Trachea (primary) | Tubular/cribriform | None | MUTYH |
| 26 | Subset | Lung (metastasis) | Tubular/cribriform | None | PIK3CA, RUNX1 |
| 27 | Subset | Lung (metastasis) | Tubular/cribriform | None | ARID2 |
| 28 | Subset | Lung (metastasis) | Tubular/cribriform | None | NRAS, ARID1A, KDM6A |
| 29 | Subset | Parotid (primary) | Solid | None | None |
Average read coverage, NOTCH1: exon 25, 106 (range 35–230); exon 26, 98 (range 28–216); exon 27, 146 (range 50–291); exon 28, 94 (range 27–242); exon 34, 94 (range 31–213)