Journal: Nature Communications

Article Title: Genomic and transcriptomic landscape of human gastrointestinal stromal tumors

doi: 10.1038/s41467-024-53821-1

Figure Lengend Snippet: a Integrated plots of clinical and genomic alterations in 78 GISTs from 68 patients. The middle panel shows selected mutated genes and variant types. Known driver genes of GIST and recurrently mutated genes detected in at least 3 patients are included. The mutation frequency of each gene is shown as a bar plot on the left with the number of affected cases labeled in parentheses. The corresponding GO biological process for each gene are shown as colored blocks on the right. Blue annotations on the right indicate whether the genes are in the Cancer Gene Census (CGC) list. The bottom panel shows selected focal CNV genes detected by GISTIC2.0. The copy number: CN = 0 indicates a Deep Deletion, CN = 1 indicates a Shallow Deletion, CN = 3 indicates a Gain and ≥4 indicates an Amplification. The red gene symbols indicate known GIST drivers. b Bar plots illustrating relative proportion of recurrently mutated genes (top) and copy number alterations (bottom) by different risk. c Lollipop plots showing the distribution of all non-silent mutations in KIT , PDGFRA , and YLPM1 . The scale bars represent the length (amino acids) of the protein sequence and the protein domains of the gene are indicated by colors. The number in parentheses denotes the number of patients. d 96-mutation spectrum of KIT mutations in GISTs. A total of 59 SNVs are identified in 46 GISTs. The distributions of KIT mutations are different from the overall SNV distributions, showing T > C and T > A bias. Source data are provided as a Source Data file.

Article Snippet: We used primary antibodies against CD117 (ready for use; Maixin Bio Co., Ltd., Fuzhou, China), SDHB (ready for use; Maixin Bio Co., Ltd., Fuzhou, China), YLPM1 (1:400; Novus Biologicals, #NBP2-22326) and CD8 (ready for use; Maixin Bio Co., Ltd., Fuzhou, China).

Techniques: Variant Assay, Mutagenesis, Labeling, Amplification, Sequencing

Journal: Nature Communications

Article Title: Genomic and transcriptomic landscape of human gastrointestinal stromal tumors

doi: 10.1038/s41467-024-53821-1

Figure Lengend Snippet: a Multiple tumors from the same patients share the same YLPM1 mutation. b Summary of YLPM1 genomic and protein aberrations in 73 GISTs. c YLPM1 protein inactivation is demonstrated by immunoblotting of GIST biopsies. YLPM1 wild-type GIST48 and GIST-T1 cell lines are used as positive controls. YLPM1 inactivation is defined by relative expression level (YLPM1/GAPDH) < 0.3, normalized to GIST-T1. All panels represent data from 3 times independent experiments. d Hematoxylin and eosin stains (bottom) and YLPM1 immunohistochemistry (IHC) stains (top): case 94 with wild-type YLPM1 shows retained YLPM1 expression; case 104 with YLPM1 frameshift mutation shows a loss of YLPM1 expression. e Summary of YLPM1 expression assessed by IHC in tissue microarrays validation cohort. f – m Restoration of YLPM1 suppresses tumor growth and proliferation in YLPM1 -inactivated GISTs. f Sanger sequencing shows that GIST-T1 YLPM1 KO isogenic cells are successfully established. g Lentivirus-mediated YLPM1 restoration reduces the viability of GIST-T1 YLPM1 KO cells, as assessed by CellTiter-Glo viability assay. Data are presented as mean values ± s.d. n = 3. h Crystal violet staining assays show that restoration of YLPM1 suppresses cell proliferation. Representative plates (top) and mean percentage area (bottom) are shown. Data are presented as mean values ± s.d. n = 3. i Restoration of YLPM1 inhibits anchorage-independent growth. Representative plates (top) and mean colony numbers (bottom) are shown. Data are presented as mean values ± s.d. n = 3. j – l Restoration of YLPM1 suppresses the growth of GIST-T1 YLPM1 KO xenografts in nude mice. Photo images ( j ) ( n = 9 mice for Ctrl, n = 8 mice for YLPM1 restoration, note that no tumor growth in 2 mice), growth curves ( k ), and tumor weight ( l ) of transplanted tumors are shown. Error bars are the mean ± s.e.m.. m GSEA reveals that genes involved in Hallmark apoptosis gene set are upregulated in GIST-T1 YLPM1 KO group. NES, normalized enrichment score. NOM P -value, Nominal P -value. All the P values are calculated using the two-sided Student’s t test. Source data are provided as a Source Data file.

Article Snippet: We used primary antibodies against CD117 (ready for use; Maixin Bio Co., Ltd., Fuzhou, China), SDHB (ready for use; Maixin Bio Co., Ltd., Fuzhou, China), YLPM1 (1:400; Novus Biologicals, #NBP2-22326) and CD8 (ready for use; Maixin Bio Co., Ltd., Fuzhou, China).

Techniques: Mutagenesis, Western Blot, Expressing, Immunohistochemistry, Biomarker Discovery, Sequencing, Viability Assay, Staining