BIOPSY RESULTS - 1288761

kcarn0927
Posts:48

Can someone interpret the biopsy result? My husband had EGFR T790M Exon 21. Has been on Tarceva, Clovis and Tagrisso. Now will be starting carbo/alimta and by our request will be staying on Tagrisso due to brain mets stable and husband is afraid to go off the Tagrisso so will be starting the combination Tagrisso and carbo/Alimta. He has had SBRT of his primary lung mass and also SBRT for a liver met.

In the first sentence it reads no T790M mutation... does that mean no more EGFR?

There was no evidence of an EGFR T790M mutation in the submitted sample.

DISEASE ASSOCIATED MUTATIONS (see interpretation and comments):

GENE PROT
EIN CHANGE cDNA CHANGE

EGFR p.L858R c.2573T>G

TP53 p.P152Rfs*18 c.455delC

INTERPRETATION AND COMMENTS:

This is an Abnormal sequencing study that identified the following disease
associated mutations:

1. A missense mutation in EGFR at amino acid 858 converting the wild type
residue, Leucine, to Arginine in 2881 reads out of a total 10411 sequence reads
for an allele frequency of 27.67%. (Transcript ID NM_005228)

2. A deletion of 1 nucleotide, C, in TP53 in 2434 reads out of a total 8065
sequence reads for an allele frequency of 30.18%. (Transcript ID NM_000546)

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JimC
Posts: 2753

Hi cc1990,

A detailed analysis of a lab report such as this is beyond the scope of this site, but from your previous postings I can see that your husband originally had an L858R EGFR mutation in exon 21, a mutation that is associated with sensitivity to an EGFR TKI. The recent test did not detect a T790M mutation, which is in exon 21, a mutation that is associated with TKI resistance. The presence of the original exon 21 mutation continues to be seen. It may help to review Dr. Pennell's excellent post on EGFR; the second chart in that post makes clear the role of the various EGFR mutations.

Tagrisso was designed to overcome the resistance conferred by the presence of a T790M mutation, but since that mutation was not detected, if he progressed on Tarceva, then there was some other factor creating resistance. Whether Tagrisso can overcome this unknown mechanism of resistance is unclear.

JimC
Forum moderator