Examination of the difference between primary and bone metastatic lesion using comprehensive genome profiling

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18049
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido Cancer Center(Department of Clinical Research) (2021-2023); Hokkaido University (2020)
• Principal Investigator: Iwata Akira 独立行政法人国立病院機構北海道がんセンター(臨床研究部), 臨床研究部, 骨軟部腫瘍科医長 (10374373)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Bone metastasis / Genome profiling

Outline of Final Research Achievements

Comprehensive genome profiling has enabled the selection of antitumor drugs based on genetic mutations, but it is dependent on the specimens collected. Bone metastases are more likely to encompass genetic abnormalities that contribute to tumor progression and yield specimens with high tumor content. The selection of anti-tumor drugs presented by bone metastases can be expected to contribute to improved response rates to therapy. Formalin-fixed specimens from two cases of renal cell carcinoma with good nucleic acid quality and concentration in both primary and bone metastases were used. In one case, where the primary tumor was a needle biopsy and the bone metastases were surgical specimens, one sample was taken from each. In the other case, the bone metastases were heterogeneous in structure, so a total of 8 sites with different structures were collected. A comprehensive genome profiling was performed to analyze differences in gene mutations.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

原発巣は増殖の過程で腫瘍増大や浸潤及び転移の鍵となる悪性度の高い遺伝子変異が出現すると考えられる。原発巣を顕鏡すると構造が維持され比較的高分化な構造になっている部位と、構造が崩れた低分化の部位などが混ざったモザイク状の構造になっている。そのため原発巣の検体は採取部位によって腫瘍を制御するのに鍵となる遺伝子変異を包含していない場合が懸念される。一方転移病巣から採取された検体は転移をした細胞塊であり、増悪の要因となる遺伝子異常を包含している可能性が高いと期待される。骨転移巣から提示された抗腫瘍薬の選択が治療の奏効率向上に貢献することが期待できるかを、がん遺伝子パネル検査を用いて検討する。