To our knowledge, this is the first description of EBUS-TBNA samples as a platform for the generation of PDX lines. The shortcomings of PDX models, especially the lack of a host immune system, are well described. Nevertheless, increasing use of these models is driven by evidence that PDX lines retain key features of the primary tumor that are irreversibly lost in conventional tissue culture. For example, SCLC PDX lines do not respond to single agent therapy with the BCL2 antagonist ABT737 in contrast to xenograft models derived from conventional SCLC cell lines. Our data now show that SCLC PDX lines derived from EBUS-TBNA retain the characteristic features of the primary tumor. An ongoing concern with respect to PDX models is their ability to maintain the genotype of the primary tumor. Given the relatively small numbers of cells obtained from EBUS-TBNA samples, we are MK-0683 unable to determine whether the PDX genotype represents expansion of a more aggressive subclone based on the genomic heterogeneity model. Although our data clearly show that well ARRY-142886 company described driver mutations are preserved in our EBUS-TBNA PDX lines for at least 2 passages, discordance in the detection of several mutations suggests that the process of xenografting may select for genetically distinct subclones derived from highly heterogeneous primary samples. In once case, a mutation in RB1 was seen only in the PDX line, indicating that some xenograft lines may be more useful as stand alone models, rather than as identical copies of the patient��s original tumour. The amount and quality of DNA available from the EBUS sample allows for detailed, high depth sequencing analysis in contrast the more limited comparisons that can be made between circulating tumor cells and derivate PDX lines. Interestingly, the sample that generated the PDX line LX109, which grew as a LCNEC tumor, lacked mutations commonly seen in SCLC, suggesting that molecular analysis of EBUS-TBNA specimens may add to the precision of conventional pathologic and cytologic criteria. Since structural variants in genes such as MYC, MYCN and SOX2 are well described in SCLC, our approach to generating PDX lines from EBUS-TBNA specimens could also serve as a platform for more intensive interrogation using WGS analysis to determine the effects of xenografting on chromosomal instability in SCLC.