Clinicopathological characteristics and genomic profiles of RGS1 positive lymphoid neoplasms

2018 Fiscal Year Research-status Report

• Project/Area Number: 18K15100
• Research Institution: Tokai University
• Principal Investigator: カレーラス ジュアキム 東海大学, 医学部, 講師 (90637191)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: RGS1 / DLBCL / lymphoma / immune microenvironment / immune checkpoint / neoplasia

Outline of Annual Research Achievements

In this project we have focused on RGS1) which is a GTPase with a role in immune responses and expressed by the germinal centers of lymphoid follicles that has been linked to neoplasia in humans.
Our summary of research achievements are the following:
(1) We have analyzed RGS1 in Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL) and Hodgkin Lymphoma (cHL). In DLBCL (n=240 cases) cases we have found that high expression of RGS1 is associated to a poor prognosis of the patients. In FL (n=120 cases) we have found that high grade FL and transformation to DLBCL is associated with a higher expression of RGS1. In cHL (n=40 cases) we have found that the tumoral B lymphocytes are positive by RGS1 and that the immune microenvironment is also highly positive.
(2) We have correlated with several clinicopathological characteristics of the patients. Our findings show a relationship with disease progression and lack of clinical response. We have also analyzed the components of the immune microenvironment, including CD3+T lymphocytes, CD8+cytotoxic T-lymphocytes, M1-like and M2-like macrophages, etc...
(3) We are focusing on the impact of RGS1 in germinal center tridimensional structure.
(4) OncoScan is started.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

We are happy with the progress. We would like to finish the genomic analysis soon.

Strategy for Future Research Activity

We have the data of whole-genome copy number and LOH analysis using the thermofisher oncoscan platform. We have to complete the correlation between genomic changes and protein expression of several markers.
Final step would be NGS target sequencing (mutational analysis)

Research Products

• [Journal Article] Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity (2019)
  • Author(s): Tsuda Shingo、Carreras Joaquim、Kikuti YaraY、Nakae Hirohiko、Dekiden‐Monma Makiko、Imai Jin、Tsuruya Kota、Nakamura Jun、Tsukune Yoko、Uchida Tetsufumi、Matsushima Masashi、Roncador Giovanna、Suzuki Takayoshi、Nakamura Naoya、Mine Tetsuya
  • Journal Title: Pathology International Volume: - Pages: 1-12
  • DOI: 10.1111/pin.12794
  • Peer Reviewed
• [Journal Article] High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation (2019)
  • Author(s): Carreras J, Lopez-Guillermo A, Kikuti YY, Itoh J, Masashi M, Ikoma H, Tomita S, Hiraiwa S, Hamoudi R, Rosenwald A, Leich E, Martinez A, Roncador G, Villamor N, Colomo L, Perez P, Tsuji NM, Campo E, Nakamura N
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 59 Pages: 1-16
  • DOI: 10.3960/jslrt.19003
  • Peer Reviewed
• [Journal Article] Monomorphic epitheliotropic intestinal T-cell lymphoma with T-cell receptor (TCR) of silent phenotype shows rearrangement of TCRβ or TCRγ gene (2019)
  • Author(s): Tomita S, Kikuti YY, Carreras J, Nakamura N
  • Journal Title: Pathology International Volume: 69 Pages: 117-118
  • DOI: 10.1111/pin.12748
  • Peer Reviewed
• [Journal Article] Genomic Profile and Pathologic Features of Diffuse Large B-Cell Lymphoma Subtype of Methotrexate-associated Lymphoproliferative Disorder in Rheumatoid Arthritis Patients (2018)
  • Author(s): Carreras J, Yukie Kikuti Y, Miyaoka M, Hiraiwa S, Tomita S, Ikoma H, Kondo Y, Shiraiwa S, Ando K, Sato S, Suzuki Y, Miura I, Roncador G, Nakamura N
  • Journal Title: American Journal of Surgical Pathology Volume: 42 Pages: 936-950
  • DOI: 10.1097/PAS.0000000000001071
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Classical Hodgkin lymphoma-type and monomorphic-type post-transplant lymphoproliferative disorder following liver transplantation: a case report (2018)
  • Author(s): Kumata H, Nakanishi C, Murakami K, Miyagi S, Fukuhara N, Carreras J, Nakamura N, Ichinohasama R, Unno M, Kamei T, Sasano H
  • Journal Title: Surgical Case Reports Volume: 4 Pages: 72
  • DOI: 10.1186/s40792-018-0480-x
  • Peer Reviewed
• [Presentation] DLBCL subtype of MTX-LPDの臨床病理学的特徴とゲノム解析 (2018)
  • Author(s): Joaquim Carreras, Yara Yukie Kikuti, Miyaoka Masashi, Hiraiwa Shinichiro, Ikoma Haruka, Tomita Sakura, Roncador Giovanna, Naoya Nakamura
  • Organizer: 第107回日本病理学会総会
• [Presentation] Genome profile and clinicopathological characteristics of RGS1-positive Diffuse Large B-Cell Lymphoma (RGS1+DLBCL) (2018)
  • Author(s): Carreras Joaquim (カレーラス ジュアキム), 菊池 イアーラ幸江, 宮岡 雅, 加留部 謙之輔, 菰原 義弘, Bea Silvia, Hamoudi Rifat, Perez Patricia, Roncador Giovanna, Campo Elias, 中村 直哉
  • Organizer: 第58回日本リンパ網内系学会総会