WTS

Question 1

NTRK1,2,3

Answer 1

always 3’ partner with recurrent breakpoints
exons 12
exons 14

Question 2

TMPRSS2:ERG

Answer 2

should always be in prostate,
if found somewhere else:
contamination and repeat
or
the tumore is prostate and misdiagnosed

Question 3

What are the variant transcripts:

Answer 3

**ARv7 **(Prostate, breast, female genitary tumors and Salivary gland tumors)- if found outside repeat

EGFRvIII (Glioblastoma) -if found outside contamination

MET exon14 skipping (Lung)- we see low level commonly in the flowcell above threshold with some degree of frequency and that can typically be more relevant to the fact that you can get some low level of miss-splicing of MET that happens and we can pick up. What to do: if it is not in lung and if there is no mutation in MET that causes exon 14 skipping and we have less than 10 junction reads we delete it and make indeterminant. The real one usually have very high read counts

Question 4

ESR1

Answer 4

only inframe fusions in exons 5 and 6 (DNA binding domain) otherwise demote

Question 5

FGFR2 and FGFR3

Answer 5

always 5’ partner
always break at exon 17 (FGFR3 sometimes break at exon 18)

Question 6

FGFR1

Answer 6

Can be 5’ or 3’ partner behaves differently from other FGFRs

Question 7

Points to consider for inframe or out of frame

Answer 7

anytime one of the breakpoints is annotated as noncoding (eg intronic or 5’ or 3’UTR) always is going to call it out of frame, those we need to manually review to confirm they are out of frame.

Question 8

For what fusions do we paste in the geneticist box?

Answer 8

targetable kinase fusions that are pathogenic:
* FGFR2 and FGFR3
* NTRKs
* ALK
* ROS1
* RET
* Fusions that are very specific to a tumor type: euensarcoma fusions, TMPRSS2:ERG, any fusions that are for soft tissues

Question 9

NOTCH2

Answer 9

We freport Oof because Oof fusions predicted to use an alternate translation start and lack a gamma secretase site