Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors

Hirokazu Takami; Kaishi Satomi; Kohei Fukuoka; Taishi Nakamura; Shota Tanaka; Akitake Mukasa; Nobuhito Saito; Tomonari Suzuki; Takaaki Yanagisawa; Kazuhiko Sugiyama; Masayuki Kanamori; Toshihiro Kumabe; Teiji Tominaga; Kaoru Tamura; Taketoshi Maehara; Masahiro Nonaka; Akio Asai; Kiyotaka Yokogami; Hideo Takeshima; Toshihiko Iuchi; Keiichi Kobayashi; Koji Yoshimoto; Keiichi Sakai; Yoichi Nakazato; Masao Matsutani; Motoo Nagane; Ryo Nishikawa; Koichi Ichimura

doi:10.1038/s41598-023-42842-3

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors

Sci Rep. 2023 Sep 21;13(1):15760. doi: 10.1038/s41598-023-42842-3.

Authors

Hirokazu Takami¹, Kaishi Satomi², Kohei Fukuoka³, Taishi Nakamura⁴, Shota Tanaka⁵, Akitake Mukasa^{5

6}, Nobuhito Saito⁵, Tomonari Suzuki⁷, Takaaki Yanagisawa⁸, Kazuhiko Sugiyama⁹, Masayuki Kanamori¹⁰, Toshihiro Kumabe^{10

11}, Teiji Tominaga¹⁰, Kaoru Tamura¹², Taketoshi Maehara¹², Masahiro Nonaka¹³, Akio Asai¹³, Kiyotaka Yokogami¹⁴, Hideo Takeshima¹⁴, Toshihiko Iuchi¹⁵, Keiichi Kobayashi¹⁶, Koji Yoshimoto¹⁷, Keiichi Sakai¹⁸, Yoichi Nakazato¹⁹, Masao Matsutani²⁰, Motoo Nagane¹⁶, Ryo Nishikawa⁷, Koichi Ichimura²¹

Affiliations

¹ Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. takami-tky@umin.ac.jp.
² Department of Pathology, Kyorin University Faculty of Medicine, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan.
³ Departments of Hematology/Oncology, Saitama Children's Medical Center, 1-2, Shintoshin, Chuo-ku, Saitama City, Saitama, 330-8777, Japan.
⁴ Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama City, Kanagawa, 236-0004, Japan.
⁵ Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
⁶ Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
⁷ Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka City, Saitama, 350-1298, Japan.
⁸ Department of Neurosurgery, Jikei University, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
⁹ Department of Clinical Oncology and Neuro-Oncology Program, Faculty of Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
¹⁰ Department of Neurosurgery, Tohoku University School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai City, Miyagi, 980-8574, Japan.
¹¹ Department of Neurosurgery, Kitasato University, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa, 252-0374, Japan.
¹² Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-0034, Japan.
¹³ Department of Neurosurgery, Kansai Medical University Hospital, 2-3-1, Shinmachi, Hirakata City, Osaka, 573-1191, Japan.
¹⁴ Department of Neurosurgery, University of Miyazaki Faculty of Medicine, 5200, Kihara, Kiyotakecho, Miyazaki, 889-1692, Japan.
¹⁵ Department of Neurosurgery, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-0801, Japan.
¹⁶ Department of Neurosurgery, Kyorin University Faculty of Medicine, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan.
¹⁷ Department of Neurosurgery, Kyusyu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
¹⁸ Shinshu Ueda Medical Center, 1-27-21, Midorigaoka, Ueda City, Nagano, 386-8610, Japan.
¹⁹ Department of Pathology, Hidaka Hospital, 886, Nakaomachi, Takasaki City, Gunma, 370-0001, Japan.
²⁰ Gotanda Rehabilitation Hospital, 8-20, Nishi-gotanda, Shinagawa-ku, Tokyo, 141-0031, Japan.
²¹ Department of Brain Disease Translational Research, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Abstract

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Central Nervous System
Central Nervous System Neoplasms* / genetics
DNA Copy Number Variations
Germinoma*
Humans
Neoplasms, Germ Cell and Embryonal* / genetics