TY - JOUR
T1 - Intratumoral genomic heterogeneity may hinder precision medicine strategies in patients with serous ovarian carcinoma
AU - Nakamura, Kohei
AU - Aimono, Eriko
AU - Tanishima, Shigeki
AU - Imai, Mitsuho
AU - Nagatsuma, Akiko Kawano
AU - Hayashi, Hideyuki
AU - Yoshimura, Yuki
AU - Nakayama, Kentaro
AU - Kyo, Satoru
AU - Nishihara, Hiroshi
N1 - Funding Information:
Funding: This study was supported by the JSPS KAKENHI (Grant-in-Aid for Young Scientists B) Grant Number 20K18232, and the Japan Agency for Medical Research and Development (AMED) under grant number JP 16kk0205006.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/4
Y1 - 2020/4
N2 - Precision medicine, which includes comprehensive genome sequencing, is a potential therapeutic option for treating high-grade serous carcinoma (HGSC). However, HGSC is a heterogeneous tumor at the architectural, cellular, and molecular levels. Intratumoral molecular heterogeneity currently limits the precision of medical strategies based on the gene mutation status. This study was carried out to analyze the presence of 160 cancer-related genetic alterations in three tissue regions with different pathological features in a patient with HGSC. The patient exhibited histological heterogeneous features with different degrees of large atypical cells and desmoplastic reactions. TP53 mutation, ERBB2 and KRAS amplification, and WT1, CDH1, and KDM6A loss were detected as actionable gene alterations. Interestingly, the ERBB2 and KRAS amplification status gradually changed according to the region examined. The difference was consistent with the differences in pathological features. Our results demonstrate the need for sampling of the appropriate tissue region showing progression of pathological features for molecular analysis to solve issues related to tumor heterogeneity prior to developing precision oncology strategies.
AB - Precision medicine, which includes comprehensive genome sequencing, is a potential therapeutic option for treating high-grade serous carcinoma (HGSC). However, HGSC is a heterogeneous tumor at the architectural, cellular, and molecular levels. Intratumoral molecular heterogeneity currently limits the precision of medical strategies based on the gene mutation status. This study was carried out to analyze the presence of 160 cancer-related genetic alterations in three tissue regions with different pathological features in a patient with HGSC. The patient exhibited histological heterogeneous features with different degrees of large atypical cells and desmoplastic reactions. TP53 mutation, ERBB2 and KRAS amplification, and WT1, CDH1, and KDM6A loss were detected as actionable gene alterations. Interestingly, the ERBB2 and KRAS amplification status gradually changed according to the region examined. The difference was consistent with the differences in pathological features. Our results demonstrate the need for sampling of the appropriate tissue region showing progression of pathological features for molecular analysis to solve issues related to tumor heterogeneity prior to developing precision oncology strategies.
KW - DNA sequencing
KW - Genomic heterogeneity
KW - Ovarian carcinoma
KW - Precision medicine
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U2 - 10.3390/diagnostics10040200
DO - 10.3390/diagnostics10040200
M3 - Article
AN - SCOPUS:85083340217
SN - 2075-4418
VL - 10
JO - Diagnostics
JF - Diagnostics
IS - 4
M1 - 200
ER -
