Mutational profile of primary breast diffuse large B-cell lymphoma

// Fernando Franco 1, 2 , Julia Gonzalez-Rincon 3, 4 , Javier Lavernia 2, 5 , Juan F. Garcia 6 , Paloma Martin 4, 7 , Carmen Bellas 4, 7 , Miguel A. Piris 4, 8 , Lucia Pedrosa 3 , Jose Miramon 2, 9 , Jose Gomez-Codina 2, 10 , Delvys Rodriguez-Abreu 2, 11 , Isidro Machado 12 , Carmen Illueca 12 , Jesus Alfaro 2, 13 , Mariano Provencio 1, 2, * and Margarita Sanchez-Beato 2, 3, * 1 Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain 2 GOTEL (Spanish Lymphoma Oncology Group), Madrid, Spain 3 Group of Research in Lymphomas, Medical Oncology Department, Instituto de Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain 4 Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Madrid, Spain 5 Medical Oncology Department, Instituto Valenciano de Oncologia, Valencia, Spain 6 Pathology Department, MD Anderson Cancer Center, Madrid, Spain 7 Pathology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain 8 Pathology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain 9 Medical Oncology Department, Hospital Serrania de Ronda, Malaga, Spain 10 Medical Oncology Department, Hospital Universitari i Politecnic La Fe, Valencia, Spain 11 Medical Oncology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain 12 Pathology Department, Instituto Valenciano de Oncologia, Valencia, Spain 13 Medical Oncology Department, Instituto Oncologico de Kutxa, Donostia, Spain * Joint senior authors Correspondence to: Margarita Sanchez-Beato, email: msbeato@idiphim.org Keywords: primary breast lymphoma; diffuse large B-cell lymphoma; cell of origin; NFkB pathway; PIM1 Received: August 09, 2017 Accepted: October 03, 2017 Published: October 24, 2017 ABSTRACT Primary breast lymphoma is a rare form of extra-nodal lymphoid neoplasm. The most common histological type is the diffuse large B-cell lymphoma, which represents 60–80% of all the cases. Our study analyzes the mutational profile of the primary lymphoma of the breast through targeted massive sequencing with a panel of 38 genes in a group of 17 patients with primary breast diffuse large B-cell lymphoma. Seventy-point-five percent of the patients presented with stage IE and 29.5% with stage IIE. 44% of the cases correspond to lymphomas with germinal center phenotype and 33.3% to activated B-cell. The genes with a higher mutational frequency include PIM1 (in 50% of the analyzed samples), MYD88 (39%), CD79B, PRDM1 and CARD11 (17%), KMT2D , TNFIAP3 and CREBBP (11%). The profile of mutant genes involves mostly the NFκB signaling pathway. The high frequency of mutations in PIM1 compared with other lymphomas may have implications in the clinical presentation and evolution of this type of lymphoma.