Inherited Germline T790M Mutation and Somatic Epidermal Growth Factor Receptor Mutations in Non-small Cell Lung Cancer Patients

Abstract

No abstract available

Germ-line exon 21 EGFR mutations, V843I and P848L, in nonsmall cell lung cancer patients

“…Germ-line T790M mutation has been documented in five cases of four families with lung cancer susceptibility, including one family with six family members in three generations having lung cancer [4][5][6][7]. Unlike one of our cases, the germ-line V843I mutation has been reported in a family with lung cancer [10] and in a family with other cancer susceptibility [9].…”

“…Germ-line EGFR variants have rarely been described (,1 in 1000 EGFR mutations), and concern four EGFR mutations in two exons: the T790M [4][5][6][7] and R776X [3,8] in exon 20, and the V843I [9,10] and P848L [11,12] in exon 21. Although somatic T790M mutations are common in patients with acquired resistance to EGFR-TKIs (50%), germ-line EGFR T790M mutations are rare, even in never-smokers (0.54%) [7].…”

Hereditary Lung Cancer Syndrome Targets Never Smokers with Germline EGFR Gene T790M Mutations

“…Our review of the literature was complicated by double reporting of some cases, 13,19 deliberate alteration of some patient data for confidentiality reasons, 13 and by incorrect or difficult to interpret data from another report (see Supplemental data). 20 …”

“…The presence of the T790M mutation (with or without being accompanied by a more typical activating mutation at presentation predicts for resistance to the standard TKIs. The only germline cases reported to have received TKI therapy were the two sisters reported by Tibaldi et al, 20 who had partial responses. Thus in the absence of another known or suspected molecular target, conventional chemotherapy appears to be the preferred first line therapy option.…”

Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR

“…For instance, mutations that involve insertions at exon 20 impart resistance to the EGFR-TKIs. Nearly half the drug-resistant NSCLC patients possess the T790M mutation in exon 20 of EGFR, which has been considered the main cause of drug resistance [19]. A secondary mutation at T790M in EGFR has also been associated with drug resistance, as well as Met amplification [20].…”