Cancer Management and Research (Apr 2022)

The Potential Role of Genomic Signature in Stage II Relapsed Colorectal Cancer (CRC) Patients: A Mono-Institutional Study

  • Roberto M,
  • Arrivi G,
  • Pilozzi E,
  • Montori A,
  • Balducci G,
  • Mercantini P,
  • Laghi A,
  • Ierinò D,
  • Panebianco M,
  • Marinelli D,
  • Tomao S,
  • Marchetti P,
  • Mazzuca F

Journal volume & issue
Vol. Volume 14
pp. 1353 – 1369

Abstract

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Michela Roberto,1 Giulia Arrivi,2 Emanuela Pilozzi,3 Andrea Montori,3 Genoveffa Balducci,4 Paolo Mercantini,4 Andrea Laghi,5 Debora Ierinò,2 Martina Panebianco,2 Daniele Marinelli,6 Silverio Tomao,1 Paolo Marchetti,2 Federica Mazzuca2 1Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology Unit A, Policlinico Umberto I, “Sapienza” University of Rome, Rome, Italy; 2Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant’ Andrea University Hospital, Rome, Italy; 3Department of Clinical and Molecular Medicine, Sapienza University of Rome, Anatomia Patologica Unit, Sant’ Andrea University Hospital, Rome, Italy; 4Department of Medical-Surgical Sciences and Translation Medicine, Sapienza University of Rome, Gastro-intestinal Surgery Unit, Sant’ Andrea University Hospital, Rome, Italy; 5Department of Medical-Surgical Sciences and Translation Medicine, Sapienza University of Rome, Radiology Unit, Sant’ Andrea University Hospital, Rome, Italy; 6Medical Oncology Unit B, Policlinico Umberto I, Sapienza University, Rome, ItalyCorrespondence: Giulia Arrivi, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant’ Andrea University Hospital, Via di Grottarossa 1035-1039, Rome, 00189, Italy, Tel +39 3387231524, Fax +39 0633776629, Email [email protected]: The absolute benefit of adjuvant chemotherapy in stage II CRC is only 3– 4%. The identification of biomarkers through molecular profiling could identify patients who will more benefit from adjuvant chemotherapy.Patients and Methods: This retrospective analysis examined tissue blocks from 17 patients affected by relapsed stage II CRC, whose comprehensive genomic profiling of tumors was conducted through next-generation sequencing (NGS) via Roche-FoundationOne®.Results: Mutations were found in APC (76.5%), TP53 (58.8%) and KRAS (52.9%). Only KRAS wild-type samples showed FBXW7. APC frameshift mutations and MLH1 splice variant were conversely significant correlated (7% v 93%, P = 0.014). The median number of gene mutations reported was 6 (range 2– 14). The TP53 mutation was associated most frequently with lung metastasis (P = 0.07) and high tumor budding (P = 0.03). Despite no statistical significance, lung recurrence, LVI/Pni, MSI and more than 6 genetic mutations were correlated to worse DFS and OS. Patients carried co-mutations of TP53-FBXW7 reported the worse DFS (4 v 14 months) and OS (4 v 65 months) compared to the other patients.Conclusion: According to the present analysis, the setting of relapsed CRC emerges as one of the fields of greatest utility for NGS, looking at personalized cancer care.Keywords: next-generation sequencing, NGS, colon cancer, stage II, biomarkers

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