Research Papers:

Gene aberration profile of tumors of adolescent and young adult females

Yasuyuki Kanke, Akihiko Shimomura, Motonobu Saito, Takayuki Honda, Kouya Shiraishi, Yoko Shimada, Reiko Watanabe, Hiroshi Yoshida, Masayuki Yoshida, Chikako Shimizu, Kazuaki Takahashi, Hirohiko Totsuka, Hideaki Ogiwara, Sou Hirose, Koji Kono, Kenji Tamura, Aikou Okamoto, Takayuki Kinoshita, Tomoyasu Kato and Takashi Kohno _

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Oncotarget. 2018; 9:6228-6237. https://doi.org/10.18632/oncotarget.23765

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Yasuyuki Kanke1,2, Akihiko Shimomura3, Motonobu Saito1,2, Takayuki Honda1, Kouya Shiraishi1, Yoko Shimada1, Reiko Watanabe4, Hiroshi Yoshida4, Masayuki Yoshida4, Chikako Shimizu3, Kazuaki Takahashi1,5, Hirohiko Totsuka6, Hideaki Ogiwara1, Sou Hirose1,5, Koji Kono2, Kenji Tamura3, Aikou Okamoto5, Takayuki Kinoshita7, Tomoyasu Kato8 and Takashi Kohno1

1Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan

2Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan

3Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

4Pathology Division, Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan

5Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

6StaGen Co., Ltd., Tokyo, Japan

7Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan

8Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan

Correspondence to:

Takashi Kohno, email: [email protected]

Keywords: adolescent and young adult (AYA); breast tumor; ovarian tumor; mutational signature; actionable gene

Received: August 09, 2017    Accepted: September 21, 2017    Published: December 29, 2017


There has been little improvement in the prognosis for adolescent and young adult (AYA) tumor patients. Hence, there is an urgent need to understand the etiology of tumor development and identify actionable gene aberrations to improve prevention and therapy. Here, 76 sporadic tumors (48 breast, 22 ovarian, and six uterine) from 76 AYA females (age range, 25–39 years) were subjected to whole exome and RNA sequencing to determine their mutational signatures and actionable gene profiles. Two individuals with breast cancer (4.2% of cases) and one with ovarian cancer (5.3% of cases) carried germline BRCA2 mutations. The two cases with breast tumors also each carried an additional deleterious germline mutation: one in TP53 and the other in CHEK2. Mutational signature analysis of the 76 tumors indicated that spontaneous deamination of 5-methylcytosine and activity of the APOBEC cytidine deaminase protein family are major causes of mutagenesis. In addition, 18 breast or ovarian tumors (18/70, 26%), including the three cases with germline BRCA2 mutations, exhibited a predominant “BRCAness” mutational signature, an indicator of functional BRCA1/BRCA2 deficiency. Actionable aberrations and high tumor mutation burdens were detected in 24 breast (50%), 17 ovarian (77%), and five uterine (83%) tumor cases. Thus, mutational processes and aberrant genes in AYA tumors are largely shared with those identified in non-AYA tumors. The efficacy of molecular targeting and immune checkpoint inhibitory therapies should be explored for both AYA and non-AYA patients.

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