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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