case_images: PMC9792468_01
case_images: Pathology features and genetic aberrations present before and after SCLC transformation. (A) A brief history of the disease diagnosis and treatment in this patient. (B) HE and IHC staining of the tumor tissue before (first biopsy) and after (second biopsy) the SCLC transformation (10x). Scale bar indicates 200mum. (C) Genetic aberrations detected in the first and second tumor biopsy tissue using the targeted sequencing covering 56 lung cancer related genes. (D)
  MYC copy number (CN=55, upper) and EGFR copy number (CN=4.2) determined by modeling copy number variation and aneuploidy across the genome, the Y axis is indicated as log2 scale. (E) Example of MYC amplification detected by FISH in the primary LUAD (upper) and transformed SCLC (lower) tissue (40x). (F) IHC staining pattern of TP53 and RB-1 in the LUAD biopsy before transformation (10x). Scale bar indicates 200mum.
case_images: fendo-13-1006480-g001.jpg
case_images: PMC9792468_01_fendo-13-1006480-g001.jpg
case_images: f1
case_images: The percentage of Ki-67 expression positive cells increased to about 90% ( Figures 1A, B ). Targeted capture sequencing of 56 lung cancer related genes (Burning Rock Dx, Guangzhou China) revealed following mutations: EGFR p.L858R (56.7%) and NM_005228.5(EGFR):c.2126A>C (p.Glu709Ala) (EGFR p.E709A, 56.7%), NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) (PIK3CA p.E545K, 53.1%), NM_000321.2 (RB1): c.365-1G>A (RB1 c.365-1G>A, 92.1%) and NM_000546.6(TP53):c.476C>A (p.Ala159Asp) (TP53 p.A159D, 93.98%), as well as copy number changes in MYC (CN=55). This revealed a similar mutational profile in the diagnostic tissue sample with the presence of RB1 c.365-1G>A and the TP53 p.A159D in addition to the EGFR p.L858R and p.E709A.Amplification in EGFR (CN=4.2), instead of MYC, was observed in the diagnostic LUAD sample ( Figures 1C, D ). Subsequent fluorescence in situ hybridization (FISH) confirmed the MYC amplification in the SCLC sample, while the diagnostic sample did not have the MYC amplification ( Figure 1E ). Additional immunohistochemistry revealed a positive staining for TP53MUT (MAB-0674, Maixin Biotech., Fuzhou China) and negative staining for RB1 (MAB-0186, Maixin Biotech., Fuzhou China) on both the LUAD and transformed SCLC samples, consistent with the loss of function mutations caused by the TP53 p.A159D and the RB1 c.365-1G>A which leads to loss of a splice site ( Figure 1F ;  Supplementary Figure 1 ).