TY - JOUR
T1 - Clinical implications of next-generation sequencing-based panel tests for malignant ovarian tumors
AU - Saotome, Keiko
AU - Chiyoda, Tatsuyuki
AU - Aimono, Eriko
AU - Nakamura, Kohei
AU - Tanishima, Shigeki
AU - Nohara, Sachio
AU - Okada, Chihiro
AU - Hayashi, Hideyuki
AU - Kuroda, Yuka
AU - Nomura, Hiroyuki
AU - Susumu, Nobuyuki
AU - Iwata, Takashi
AU - Yamagami, Wataru
AU - Kataoka, Fumio
AU - Nishihara, Hiroshi
AU - Aoki, Daisuke
N1 - Publisher Copyright:
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing-based panel tests, including 160 cancer-related genes (PleSSision-160), on 88 malignant ovarian tumors (high-grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high-grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high-grade serous carcinoma (P <.005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P <.05) and worse survival (P <.01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P <.05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients.
AB - Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing-based panel tests, including 160 cancer-related genes (PleSSision-160), on 88 malignant ovarian tumors (high-grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high-grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high-grade serous carcinoma (P <.005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P <.05) and worse survival (P <.01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P <.05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients.
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U2 - 10.1002/cam4.3383
DO - 10.1002/cam4.3383
M3 - Article
C2 - 32813918
AN - SCOPUS:85089549398
SN - 2045-7634
VL - 9
SP - 7407
EP - 7417
JO - Cancer Medicine
JF - Cancer Medicine
IS - 20
ER -