Excited to share our analysis of 3,600 “real world” cases of Small Cell Lung Cancer (SCLC) – Christine M. Lovly
Out now in Cancer Discovery– excited to share our analysis of 3,600 “real world” cases of Small Cell Lung Cancer (SCLC).
➡ Genomic analysis of *3,600* patients with SCLC; largest SCLC study to date!
➡ Multiple interesting findings, summarized in the figure
➡ Link to the manuscript in the comments section of this post.
What makes this study unique?
1) The SCLC cohort studied came mostly from community sites – representing a more typical “real-world” cohort of SCLC.
2) The genomic data are tied to clinical data, key parameters that aren’t included in most previous SCLC genomic studies.
3) To the best of our knowledge, our study analyzes the largest number of SCLC tumors from African ancestry to date – 7.1% of the entire cohort.
4) Given the large sample size, we were able to study SCLC genomics by metastatic site. This has not been done before.
5) Further, our study contains the largest cohort studied of putative “transformed SCLC” (t-SCLC): n=121, including 107 EGFR-mutant SCLC cases.
What did we learn? (see Figure below)
1) We define a cohort of TP53/RB1 wild-type SCLC tumors
– ~5% of all SCLC
2) We identify recurrent STK11 mutations in SCLC, which are enriched in patients of AFR ancestry.
– Pts with STK11 mutations have poorer OS compared with the STK11 WT cohort.
3) We present the 1st analysis of SCLC genomics broken down by anatomical location, with a particular focus on brain metastases
– SCLC brain metastases: have higher TMB and are enriched for PTEN mutations compared to primary tumors or liver metastases
4) We identify rare SCLC tumors containing HPV DNA.
– enriched within the cohort of TP53/RB1 WT SCLC tumors
5) We analyze a large cohort (n=121) of putative tSCLC w/ driver mutations typically found in patients with NSCLC
– EGFR (ex19del >> L858R in SCLC cases!)
– ALK
– ROS1
– RET
– NTRK
– Implies need for rebiopsy of all driver mutation + NSCLC at the time of disease progression to look for SCLC transformation Limitations:
– DNA sequencing was performed on a limited number of genes (~324).
– We were not able to interrogate RNA or protein expression.
– We were not able to validate our analysis of new or rare alterations in cell or animal models. One exception is TSC1, which shows alterations in ~1% of cases in our cohort, and that was recently validated in mouse models and human cells as a potent tumor suppressor in SCLC (see PMID: 36640300).
Overall, we hope that this paper is a resource for scientists exploring various aspects of SCLC biology and the biology of other types of neuroendocrine tumors.
For details: Click here