Dataset Information

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

ABSTRACT: This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median age: 63 y). The tumors involved the right (n=12) and left colon unequally and were either stage T3 (n=12) or T4. Local lymph node and distant metastases were seen at presentation in 6 and 1 patients, respectively. Lymphovascular invasion was present in all cases. Histologically, tumors showed moderate to poor (n=11) differentiation with a partly or entirely solid pattern (n=5) and mucinous component (n=10), including 1 case with sheets of signet ring cells. DNA mismatch repair-deficient phenotype was seen in 13 cases. Tumor-infiltrating CD4/CD8 lymphocytes were prominent in 9 cases. Programmed death-ligand 1 positive tumor-infiltrating immune cells and focal tumor cell positivity were seen in the majority of cases. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 cases. No mutations in BRAF, RAS, and PIK3CA were identified. However, other genes of the PI3K-AKT/MTOR pathway were mutated. In several cases, components of Wnt/β-catenin (APC, AMER1, CTNNB1), p53, and TGFβ (ACVR2A, TGFBR2) pathways were mutated. However, no SMAD4 mutations were found. Two tumors harbored FBXW7 tumor suppressor gene mutations. NTRK fusion tumors constitute a distinct but rare subgroup of colorectal carcinomas.

SUBMITTER: Lasota J

PROVIDER: S-EPMC8170835 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

Lasota Jerzy J Chłopek Małgorzata M Lamoureux Jennifer J Christiansen Jason J Kowalik Artur A Wasąg Bartosz B Felisiak-Gołąbek Anna A Agaimy Abbas A Biernat Wojciech W Canzonieri Vincenzo V Centonze Giovanni G Chmielik Ewa E Daum Ondrej O Dubová Magdalena M Dziuba Ireneusz I Goertz Sebastian S Góźdź Stanisław S Guttmejer-Nasierowska Anna A Haglund Caj C Hałoń Agnieszka A Hartmann Arndt A Inaguma Shingo S Iżycka-Świeszewska Ewa E Kaczorowski Maciej M Kita Paweł P Kołos Małgorzata M Kopczyński Janusz J Michal Michal M Milione Massimo M Okoń Krzysztof K Pęksa Rafał R Pyzlak Michał M Ristimäki Ari A Ryś Janusz J Szostak Blażej B Szpor Joanna J Szumiło Justyna J Teresiński Leszek L Waloszczyk Piotr P Wejman Jarosław J Wesołowski Wojciech W Miettinen Markku M

The American journal of surgical pathology 20200201 2

This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median ag ...[more]

PMID: 31567189

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Dataset Information

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

Publications

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

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