PubMed:24496003
Annnotations
PubMed_Structured_Abstracts
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 80-265 | BACKGROUND | denotes | The aim of this study was to identify anaplastic lymphoma kinase (ALK) rearrangements in lung cancer patient-derived xenograft (PDX) models and to explore their responses to crizotinib. |
| T2 | 275-944 | METHODS | denotes | Screening of 99 lung cancer PDX models by the NanoString ALK fusion assay identified two ALK-rearranged non-small-cell lung cancer (NSCLC) tumors, including one harboring a previously known echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion and another containing an unknown ALK fusion variant. Expression array, RNA-Seq, reverse transcription polymerase chain reaction, and direct sequencing were then conducted to confirm the rearrangements and to identify the novel fusion partner in the xenograft and/or the primary patient tumor. Finally, pharmacological studies were performed in PDX models to evaluate their responses to ALK inhibitor crizotinib. |
| T3 | 954-1607 | RESULTS | denotes | Two ALK-rearranged NSCLC PDX models were identified: one carried a well-known EML4-ALK variant 3a/b and the other harbored a novel huntingtin interacting protein 1 (HIP1)-ALK fusion gene. Exon 28 of the HIP1 gene located on chromosome 7 was fused to exon 20 of the ALK gene located on chromosome 2. Both cases were clinically diagnosed as squamous cell carcinoma. Compared with the other lung cancer PDX models, both ALK-rearranged models displayed elevated ALK mRNA expression. Furthermore, in vivo efficacy studies demonstrated that, similar to the EML4-ALK-positive model, the HIP1-ALK-containing PDX model was sensitive to treatment with crizotinib. |
| T4 | 1621-1972 | CONCLUSIONS | denotes | Discovery of HIP1 as a fusion partner of ALK in NSCLC is a novel finding. In addition, the HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib in vivo, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis. Collectively, our results indicate that HIP1-ALK-positive NSCLC may benefit from clinical applications of crizotinib. |
DisGeNET
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T0 | 1634-1638 | gene:3092 | denotes | HIP1 |
| T1 | 1669-1674 | disease:C0007131 | denotes | NSCLC |
| T2 | 1662-1665 | gene:238 | denotes | ALK |
| T3 | 1669-1674 | disease:C0007131 | denotes | NSCLC |
| R1 | T0 | T1 | associated_with | HIP1,NSCLC |
| R2 | T2 | T3 | associated_with | ALK,NSCLC |
PubmedHPO
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 129-137 | HP_0002665 | denotes | lymphoma |
| T2 | 169-180 | HP_0100526 | denotes | lung cancer |
| T3 | 174-180 | HP_0002664 | denotes | cancer |
Allie
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| SS1_24496003_2_0 | 118-144 | expanded | denotes | anaplastic lymphoma kinase |
| SS2_24496003_2_0 | 146-149 | abbr | denotes | ALK |
| SS1_24496003_2_1 | 181-206 | expanded | denotes | patient-derived xenograft |
| SS2_24496003_2_1 | 208-211 | abbr | denotes | PDX |
| SS1_24496003_4_0 | 379-405 | expanded | denotes | non-small-cell lung cancer |
| SS2_24496003_4_0 | 407-412 | abbr | denotes | NSCLC |
| SS1_24496003_4_1 | 465-513 | expanded | denotes | echinoderm microtubule-associated protein-like 4 |
| SS2_24496003_4_1 | 515-519 | abbr | denotes | EML4 |
| SS1_24496003_8_0 | 1085-1117 | expanded | denotes | huntingtin interacting protein 1 |
| SS2_24496003_8_0 | 1119-1123 | abbr | denotes | HIP1 |
| AE1_24496003_2_0 | SS1_24496003_2_0 | SS2_24496003_2_0 | abbreviatedTo | anaplastic lymphoma kinase,ALK |
| AE1_24496003_2_1 | SS1_24496003_2_1 | SS2_24496003_2_1 | abbreviatedTo | patient-derived xenograft,PDX |
| AE1_24496003_4_0 | SS1_24496003_4_0 | SS2_24496003_4_0 | abbreviatedTo | non-small-cell lung cancer,NSCLC |
| AE1_24496003_4_1 | SS1_24496003_4_1 | SS2_24496003_4_1 | abbreviatedTo | echinoderm microtubule-associated protein-like 4,EML4 |
| AE1_24496003_8_0 | SS1_24496003_8_0 | SS2_24496003_8_0 | abbreviatedTo | huntingtin interacting protein 1,HIP1 |
DisGeNET5_gene_disease
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| 24496003-1#38#64#gene238 | 118-144 | gene238 | denotes | anaplastic lymphoma kinase |
| 24496003-1#66#69#gene238 | 146-149 | gene238 | denotes | ALK |
| 24496003-1#89#100#diseaseC0242379 | 169-180 | diseaseC0242379 | denotes | lung cancer |
| 24496003-1#89#100#diseaseC0684249 | 169-180 | diseaseC0684249 | denotes | lung cancer |
| 24496003-1#89#100#diseaseC1306460 | 169-180 | diseaseC1306460 | denotes | lung cancer |
| 24496003-1#89#100#diseaseC0242379 | 169-180 | diseaseC0242379 | denotes | lung cancer |
| 24496003-1#89#100#diseaseC0684249 | 169-180 | diseaseC0684249 | denotes | lung cancer |
| 24496003-1#89#100#diseaseC1306460 | 169-180 | diseaseC1306460 | denotes | lung cancer |
| 24496003-10#13#17#gene3092 | 1634-1638 | gene3092 | denotes | HIP1 |
| 24496003-10#48#53#diseaseC0007131 | 1669-1674 | diseaseC0007131 | denotes | NSCLC |
| 24496003-11#106#110#gene3092 | 1801-1805 | gene3092 | denotes | HIP1 |
| 24496003-11#145#158#diseaseC0596263 | 1840-1853 | diseaseC0596263 | denotes | tumorigenesis |
| 24496003-12#45#48#gene238 | 1900-1903 | gene238 | denotes | ALK |
| 24496003-12#58#63#diseaseC0007131 | 1913-1918 | diseaseC0007131 | denotes | NSCLC |
| 24496003-5#78#82#gene27436 | 1032-1036 | gene27436 | denotes | EML4 |
| 24496003-5#19#24#diseaseC0007131 | 973-978 | diseaseC0007131 | denotes | NSCLC |
| 38#64#gene23889#100#diseaseC0242379 | 24496003-1#38#64#gene238 | 24496003-1#89#100#diseaseC0242379 | associated_with | anaplastic lymphoma kinase,lung cancer |
| 38#64#gene23889#100#diseaseC0684249 | 24496003-1#38#64#gene238 | 24496003-1#89#100#diseaseC0684249 | associated_with | anaplastic lymphoma kinase,lung cancer |
| 38#64#gene23889#100#diseaseC1306460 | 24496003-1#38#64#gene238 | 24496003-1#89#100#diseaseC1306460 | associated_with | anaplastic lymphoma kinase,lung cancer |
| 38#64#gene23889#100#diseaseC0242379 | 24496003-1#38#64#gene238 | 24496003-1#89#100#diseaseC0242379 | associated_with | anaplastic lymphoma kinase,lung cancer |
| 38#64#gene23889#100#diseaseC0684249 | 24496003-1#38#64#gene238 | 24496003-1#89#100#diseaseC0684249 | associated_with | anaplastic lymphoma kinase,lung cancer |
| 38#64#gene23889#100#diseaseC1306460 | 24496003-1#38#64#gene238 | 24496003-1#89#100#diseaseC1306460 | associated_with | anaplastic lymphoma kinase,lung cancer |
| 66#69#gene23889#100#diseaseC0242379 | 24496003-1#66#69#gene238 | 24496003-1#89#100#diseaseC0242379 | associated_with | ALK,lung cancer |
| 66#69#gene23889#100#diseaseC0684249 | 24496003-1#66#69#gene238 | 24496003-1#89#100#diseaseC0684249 | associated_with | ALK,lung cancer |
| 66#69#gene23889#100#diseaseC1306460 | 24496003-1#66#69#gene238 | 24496003-1#89#100#diseaseC1306460 | associated_with | ALK,lung cancer |
| 66#69#gene23889#100#diseaseC0242379 | 24496003-1#66#69#gene238 | 24496003-1#89#100#diseaseC0242379 | associated_with | ALK,lung cancer |
| 66#69#gene23889#100#diseaseC0684249 | 24496003-1#66#69#gene238 | 24496003-1#89#100#diseaseC0684249 | associated_with | ALK,lung cancer |
| 66#69#gene23889#100#diseaseC1306460 | 24496003-1#66#69#gene238 | 24496003-1#89#100#diseaseC1306460 | associated_with | ALK,lung cancer |
| 13#17#gene309248#53#diseaseC0007131 | 24496003-10#13#17#gene3092 | 24496003-10#48#53#diseaseC0007131 | associated_with | HIP1,NSCLC |
| 106#110#gene3092145#158#diseaseC0596263 | 24496003-11#106#110#gene3092 | 24496003-11#145#158#diseaseC0596263 | associated_with | HIP1,tumorigenesis |
| 45#48#gene23858#63#diseaseC0007131 | 24496003-12#45#48#gene238 | 24496003-12#58#63#diseaseC0007131 | associated_with | ALK,NSCLC |
| 78#82#gene2743619#24#diseaseC0007131 | 24496003-5#78#82#gene27436 | 24496003-5#19#24#diseaseC0007131 | associated_with | EML4,NSCLC |