Intertumor and intratumor heterogeneity of PIK3CA mutations in extramammary Paget’s disease
Intertumor and intratumor heterogeneity of PIK3CA mutations in extramammary Paget’s disease
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乳房外佩吉特病中 PIK3CA 突变的肿瘤间和肿瘤内异质性
DOI：
10.1111/1346-8138.16343
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Masuguchi Shinic
中科院分区：
文献类型：
--
作者：
Kusaba Yudo;Kajihara Ikko;Myangat Tselmeg Mijiddorj;Tanaka Kenichiro;Sakamoto Ryoko;Maeda‐Otsuka Saki;Yamada‐Kanazawa Saori;Sawamura Soichiro;Kanemaru Hisashi;Nishimura Yuki;Nakamura‐Kashiwada Kayo;Makino Katsunari;Miyashita Azusa;Aoi Jun;Masuguchi Shinic
尽管乳腺外佩吉特病（EMPD）患者行根治性切除术预后良好，但伴有远处转移的EMPD患者的预后非常差，PIK 3CA突变预示着PIK 3CA抑制剂的良好疗效。本研究的目的是调查与EMPD肿瘤间和肿瘤内异质性相关的PIK 3CA突变（包括多突变[MM]）的发生率，并评估这些突变与EMPD临床参数之间的相关性。我们采用液滴数字聚合酶链反应检测了68例EMPD患者的PIK 3CA突变（E542 K、E545 K、H1047 R和MM）。此外，我们调查了16例PIK 3CA突变患者多个位点的PIK 3CA突变，以评估EMPD中PIK 3CA突变的瘤内异质性。EMPD患者PIK 3CA基因突变率为30.8%（21/68）。E542 K、E545 K、H1047 R和MM的频率分别为10.2%（7/68）、13.2%（9/68）、11.7%（8/68）和4.4%（3/68）。PIK 3CA突变模式与临床参数之间无显著相关性。在21例PIK 3CA突变患者中，检查了16例可在多个部位进行分析的组织样本。所有研究中心PIK 3CA突变相同的患者比例为12.5%（2/16）。在至少两个或两个以上位点（但不是所有位点）有相同PIK 3CA突变的患者比例为31.2%（5/16）。其他部位无PIK 3CA突变的患者比例为37.5%（6/16）。其他位点PIK 3CA突变的患者比例为18.7%（3/16）。PIK 3CA突变在EMPD中存在肿瘤间和肿瘤内异质性，PIK 3CA突变可能是EMPD的进展突变。
Although the prognosis of patients with extramammary Paget’s disease (EMPD) treated with radical resection is good, the prognosis of EMPD with distant metastasis is very poor.PIK3CAmutations predict a good response toPIK3CAinhibitors. The aim of this study was to investigate the occurrence rate ofPIK3CAmutations (including multiple mutations [MM]) related to the intertumor and intratumor heterogeneity in EMPD and to evaluate the correlation between these mutations and clinical parameters of EMPD. We performed droplet digital polymerase chain reaction to detectPIK3CAmutations (E542K, E545K, H1047R, and MM) in 68 patients with EMPD. In addition, we investigated the presence ofPIK3CAmutations at multiple sites in 16 patients withPIK3CAmutations to assess the intratumor heterogeneity ofPIK3CAmutations in EMPD. The frequency of one or morePIK3CAmutations in patients with EMPD was 30.8% (21/68). The frequency of E542K, E545K, H1047R, and MM were 10.2% (7/68), 13.2% (9/68), 11.7% (8/68), and 4.4% (3/68), respectively. No significant correlation was found betweenPIK3CAmutation patterns and clinical parameters. Of the 21 patients withPIK3CAmutations, 16 with tissue samples that could be analyzed at multiple sites were examined. The proportion of patients with the samePIK3CAmutations at all sites was 12.5% (2/16). The proportion of patients with the samePIK3CAmutations at least two or more sites, but not at all sites, was 31.2% (5/16). The proportion of patients with noPIK3CAmutations at other sites was 37.5% (6/16). The proportion of patients with otherPIK3CAmutations at other sites was 18.7% (3/16). There is intertumor and intratumor heterogeneity ofPIK3CAmutations.PIK3CAmutations in EMPD may be progressor mutations in EMPD.
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影响因子：
64.8
作者：
Yuki Saito;Junji Koya;Mitsugu Araki;Yasunori Kogure;Sumito Shingaki;Mariko Tabata;Marni B. McClure;Kota Yoshifuji;Shigeyuki Matsumoto;Yuta Isaka;Hiroko Tanaka;Takanori Kanai;Satoru Miyano;Yuichi Shiraishi;Yasushi Okuno;Keisuke Kataoka
通讯作者：
Keisuke Kataoka
基因组改变作为外阴乳房外佩吉特病的潜在治疗靶点。
影响因子：
4.6
作者：
M. Stasenko;G. Jayakumaran;R. Cowan;V. Broach;D. Chi;A. Rossi;T. Hollman;A. Zehir;N. Abu;M. Leitao
通讯作者：
M. Leitao
影响因子：
6.5
作者：
Riveiro-Falkenbach, Erica;Villanueva, Candida A.;Rodriguez-Peralto, Jose L.
通讯作者：
Rodriguez-Peralto, Jose L.
MUC16 (CA125) 在乳房外佩吉特病中过度表达。
影响因子：
2.4
作者：
S. Sawamura;I. Kajihara;Y. Tasaki;S. Otsuka;R. Sakamoto;S. Kanazawa;K. Makino;J. Aoi;H. Ihn
通讯作者：
H. Ihn