Distribution differences in prognostic copy number alteration profiles in IDH-wild-type glioblastoma cause survival discrepancies across cohorts

Acta Neuropathologica Communications

  ^{1    2    2    2    2    3    4    5    6    7    7    8    9    9    1,10    1,10    1,10    1,11    1,12    1,13    1,14} 

[1] 0000 0004 0373 3971, grid.136593.b, Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;0000 0004 0373 3971, grid.136593.b, Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0004 0373 3971, grid.136593.b, Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;grid.489169.b, Department of Neurosurgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, 541-8567, Osaka-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0000 9142 153X, grid.272264.7, Department of Neurosurgery, Hyogo College of Medicine, 1-1 Mukogawa, 663-8501, Nishinomiya, Hyogo, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0000 9142 153X, grid.272264.7, Department of Neurosurgery, Hyogo College of Medicine, 1-1 Mukogawa, 663-8501, Nishinomiya, Hyogo, Japan;0000 0004 0546 3696, grid.414976.9, Department of Neurosurgery, Kansai Rosai Hospital, 3-1-69, Inabasou, 660-5811, Amagasaki City, Hyogo, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0001 0667 4960, grid.272458.e, Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kamigyo-ku Kajii-cho, Kawaramachi-Hirokoji, 602-8566, Kyoto-City, Kyoto, Japan;Department of Central Laboratory and Surgical Pathology, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0001 1009 6411, grid.261445.0, Department of Neurosurgery, Osaka City University Graduate School of Medicine, 1-5-7, Asahi-machi, Abeno-ku, 545-8586, Osaka-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0001 1009 6411, grid.261445.0, Department of Neurosurgery, Osaka City University Graduate School of Medicine, 1-5-7, Asahi-machi, Abeno-ku, 545-8586, Osaka-City, Osaka, Japan;0000 0004 1936 9967, grid.258622.9, Department of Neurosurgery, Kindai University Faculty of Medicine, 337-2, Ono-higashi, 589-8511, Osaka Sayama-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;0000 0004 1763 1087, grid.412857.d, Department of Neurological Surgery, Wakayama Medical University School of Medicine, Kimiidera 811-1, 641-0012, Wakayama, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;Department of Biomedical Research and Innovation Research, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;Department of Biomedical Research and Innovation Research, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;Department of Central Laboratory and Surgical Pathology, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;0000 0001 2172 5041, grid.410783.9, Department of Neurosurgery, Kansai Medical University, 3-1 Shinmachi 2 Chome, 573-1191, Hirakata City, Osaka, Japan;Kansai Molecular Diagnosis Network for CNS Tumors, Osaka-City, Osaka, Japan;grid.489169.b, Department of Neurosurgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, 541-8567, Osaka-City, Osaka, Japan;Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, 540-0006, Osaka-City, Osaka, Japan;

关键词: Glioblastoma;    Copy number alteration;    EGFR;    CDKN2A;    PTEN;   

DOI  :  10.1186/s40478-019-0749-8

来源: publisher

【 摘 要 】

The diagnosis and prognostication of glioblastoma (GBM) remain to be solely dependent on histopathological findings and few molecular markers, despite the clinical heterogeneity in this entity. To address this issue, we investigated the prognostic impact of copy number alterations (CNAs) using two population-based IDH-wild-type GBM cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). The molecular disproportions between these cohorts were dissected in light of cohort differences in GBM. The Japanese cohort was collected from cases registered in Kansai Molecular Diagnosis Network for CNS tumors (KNBTG). The somatic landscape around CNAs was analyzed for 212 KNBTG cases and 359 TCGA cases. Next, the clinical impacts of CNA profiles were investigated for 140 KNBTG cases and 152 TCGA cases treated by standard adjuvant therapy using temozolomide-based chemoradiation. The comparative profiling indicated unequal distribution of specific CNAs such as EGFR, CDKN2A, and PTEN among the two cohorts. Especially, the triple overlap CNAs in these loci (triple CNA) were much higher in frequency in TCGA (70.5%) than KNBTG (24.3%), and its prognostic impact was independently validated in both cohorts. The KNBTG cohort significantly showed better prognosis than the TCGA cohort (median overall survival 19.3 vs 15.6 months). This survival difference between the two cohorts completely resolved after subclassifying all cases according to the triple CNA status. The prognostic significance of triple CNA was identified in IDH-wild-type GBM. Distribution difference in prognostic CNA profiles potentially could cause survival differences across cohorts in clinical studies.

【 授权许可】

CC BY