Sinonasal Tumors

Question 1

Molecular features of NUT Carcinoma

Answer 1

BRD4-NUTM1
BRD3-NUTM1
other variant NUTM1 rearrangements

Question 2

Targeted therapy for NUT carcinomas

Answer 2

Bromodomain inhibitors
HDAC inhibitors

Question 3

Molecular features of SMARCB1-deficient Sinonasal Carcinoma

Answer 3

Inactivating SMARCB1 mutations or deletions.

Inactivating mutations in SMARCB1 are often truncating, and LOH is frequent.

Question 4

Targeting SMARCB1 deficiency

Answer 4

SMARCB1 deficiency makes tumors susceptible to EZH2 inhibitors, like tazemetostat.

Question 5

Molecular features of sinonasal undifferentiated carcinoma and sinonasal LC-NEC

Answer 5

These tumors probably exist on a spectrum

Most display IDH2 R172S ot R172T, which is also detectable by a commercially available monoclonal antibody.

Question 6

Recurrent molecular features of sinonasal squamous cell carcinomas

Answer 6

EGFR/ERBB1 exon 20 insertions (suggest origin from an inverted papilloma)

KRAS hotspot mutations (suggest origin from an oncocytic papilloma)

Question 7

Molecular features of intestinal-type sinonasal adenocarcinomas

Answer 7

KRAS hotspot mutations

Question 8

Molecular features of non-intestinal type sinonasal adenocarcinomas

Answer 8

More varied than intestinal-type

ETV6::NTRK3 / ETV6::RET fusions
CTNNB1 mutations
BRAF mutations