Chiara Romano1,2, Sandra Di Gregorio3,4, Maria Stella Pennisi3,4, Elena Tirrò4,5, Giuseppe Broggi6, Rosario Caltabiano6, Livia Manzella3,4, Martino Ruggieri7, Paolo Vigneri3,4, Antonio Di Cataldo8. 1. Department of Clinical and Experimental Medicine, University of Catania, 95123, Catania, Italy. chiararomano83@gmail.com. 2. Center of Experimental Oncology and Hematology, A.O.U. Policlinico "G. Rodolico - San Marco", 95123, Catania, Italy. chiararomano83@gmail.com. 3. Department of Clinical and Experimental Medicine, University of Catania, 95123, Catania, Italy. 4. Center of Experimental Oncology and Hematology, A.O.U. Policlinico "G. Rodolico - San Marco", 95123, Catania, Italy. 5. Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, 90127, Palermo, Italy. 6. Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Section of Anatomic Pathology, University of Catania, 95123, Catania, Italy. 7. Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, 95123, Catania, Italy. 8. Department of General Surgery and Medical-Surgical Specialties, University of Catania, 95123, Catania, Italy.
Abstract
BACKGROUND: Multiple primary malignancies (MPM) are defined as tumors originating in the same individual without any correlation between them. In addition to morphological and immunohistochemical analyses, sensitive DNA sequencing methods such as next generation sequencing (NGS) may help to discriminate the common or different genetic alterations driving each malignancy, to better diagnose these uncommon cases. METHODS AND RESULTS: Here we report the case of a man who developed a poorly differentiated gastric adenocarcinoma invading the pancreas followed, two years later, by a colorectal cancer involving also the kidney and the diaphragm. Despite the advanced stage of both diseases, adjuvant chemotherapy was successful. While the second tumor was initially interpreted as a relapse of his stomach cancer, NGS-based mutation profiling of the two carcinomas revealed two distinct malignances, independently developing in different times and indicative of metachronous MPM. Indeed, sequencing of cancer-associated genes identified somatic mutations only in the first gastric cancer, besides germline variants on three different genes (PDGFRA, APC and TP53). However, analysis of both somatic and germline mutations with bio-informatics prediction tools failed to find a correlation between these variants and the unexpectedly good prognosis of both cancers. CONCLUSIONS: In summary, NGS analysis contributed to defined different molecular profiles for two tumors developed in the span of two years, thus allowing diagnosing the case as MPN. However, NGS was unable to establish a direct correlation between the identified alterations and cancer development.
BACKGROUND: Multiple primary malignancies (MPM) are defined as tumors originating in the same individual without any correlation between them. In addition to morphological and immunohistochemical analyses, sensitive DNA sequencing methods such as next generation sequencing (NGS) may help to discriminate the common or different genetic alterations driving each malignancy, to better diagnose these uncommon cases. METHODS AND RESULTS: Here we report the case of a man who developed a poorly differentiated gastric adenocarcinoma invading the pancreas followed, two years later, by a colorectal cancer involving also the kidney and the diaphragm. Despite the advanced stage of both diseases, adjuvant chemotherapy was successful. While the second tumor was initially interpreted as a relapse of his stomach cancer, NGS-based mutation profiling of the two carcinomas revealed two distinct malignances, independently developing in different times and indicative of metachronous MPM. Indeed, sequencing of cancer-associated genes identified somatic mutations only in the first gastric cancer, besides germline variants on three different genes (PDGFRA, APC and TP53). However, analysis of both somatic and germline mutations with bio-informatics prediction tools failed to find a correlation between these variants and the unexpectedly good prognosis of both cancers. CONCLUSIONS: In summary, NGS analysis contributed to defined different molecular profiles for two tumors developed in the span of two years, thus allowing diagnosing the case as MPN. However, NGS was unable to establish a direct correlation between the identified alterations and cancer development.
Authors: A Slem; R Abu-Hijlih; F Abdelrahman; R Turfa; R Amarin; N Farah; M Sughayer; A Almousa; J Khader Journal: Hematol Oncol Stem Cell Ther Date: 2011
Authors: Alexia Vogt; Sabine Schmid; Karl Heinimann; Harald Frick; Christian Herrmann; Thomas Cerny; Aurelius Omlin Journal: ESMO Open Date: 2017-05-02