At 24 weeks, 14/25 patients (56%) with baseline JAK2V617F mutation achieved a spleen response.
Forty-four percent of CML patients with the BCR-ABL T315I mutation achieved a response, and responses were reported as durable.
In that study using tumour response according to Miller Payne criteria as a surrogate end point for outcome, 2/2 TNBC patients with a BRCA1 mutation achieved a pathological complete remission (pCR) on conventionally dosed cisplatin [ 37].
Supporting this idea, mutations achieved in one single T3E rarely affect the virulence phenotype of strains.
Indeed, high-coverage whole-genome sequencing of another population founded from the same strain found that only three synonymous mutations achieved detectable frequencies in 20,000 generations [ 48].
In two patients, there were concomitant mutations of KRAS codon 146 and PIK3CA exon 9 and NRAS codon 61and PIK3CA exon 9. Patients with genomic mutations achieved no response to anti-EGFR antibodies (SD: N=6, PD: N=12).
Indeed, the response to PE would not be expected to be effective for patients with mutations in MCP, a transmembrane protein that is not removed by this treatment, but patients with combined mutations achieved remission with PE similar to patients with single non- MCP mutations [ 9].
Prophylactic immunisation with 27mer peptides encoding these mutations achieved complete tumour protection and survival in 40% of the mice, whereas all mice in the control group died within 44 days.
By this analysis, mutation profiling achieved a similarly high specificity of 99.8%.
Although CHEK2 H371Y carriers were more likely to respond to neoadjuvant chemotherapy, only small subset of mutation carriers achieved a pCR, the majority of CHEK2 H371Y carriers who did not reach a pCR might have a particularly aggressive phenotype.
