Chipping away at the cause behind rare tumors

HOUSTON - (June 2, 2014) - A new study by an international collaboration of researchers, including those from Baylor College of Medicine, has uncovered the underlying mutations in intracranial germ cell tumors, which could lead to new therapeutic targets. The findings were published in a recent edition of the journal Nature.

Intracranial germ cell tumors (GCT) are relatively rare tumors affecting children and young adults but the incidence of these tumors is about 8 to 10 times higher in Japan than in the Western world. The tumors are divided into two subgroups - germinoma and non-germinomatous germ cell tumors (NGGCT). While the prognosis of germinoma is good with long-term survival about 90 percent following treatment of surgery and radiation/chemotherapy, the prognosis for NGGCT is poor, with a survival rate of less than 25 percent.

Researchers identified frequent mutations in the KIT/RAS and AKT/mTOR signaling pathways as well as rare germline variants in JMJD1C, suggesting potential therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

"This is the first time a large series of intracranial GCTs have been genomically analyzed with next generation sequencing which shows recurrent mutations in these tumors that are potential therapeutic targets," said Dr. Ching Lau, associate professor of pediatrics at Baylor and Texas Children's Cancer Center and senior author of the paper. "In addition, this is also the first time that predisposition genes in cancer were identified by next generation sequencing. These rare variants in the Japanese patient population could potentially explain the much higher incidence of this type of tumors in that population compared to the Western world."

These results put researchers in the position to explore targeted therapy for intracranial GCTs by carrying out preclinical evaluation of various drug candidates in preparation for clinical trials, Lau said.

International collaboration in a focused study could yield very important results of rare tumors that would not be otherwise possible by individual centers.

The research was supported by funding from National Human Genome Research Institute,National Library of Medicine, Cancer Prevention and Research Institute of Texas, the Children's Brain Tumor Foundation, the Gillson Longenbaugh Foundation and Anderson Charitable Foundation, and the St. Baldrick's Foundation.

Others involved in the study include: Linghua Wang, Shigeru Yamaguchi, Matthew D. Burstein, Kyle Chang, Zongxiao He, Harshavardhan Doddapaneni, Lora Lewis, Mark Wang, Robert Dauser, William Whitehead, Adesina Adekunle, Jiayi Sun, Donna M. Muzny, Richard A. Gibbs, Suzanne M. Leal, and David A. Wheeler, all of Baylor College of Medicine; Keita Terashima, Baylor and National Center for Child Health and Development, Tokyo, Japan; Ho-Keung Ng, Chinese University of Hong Kong; Hideo Nakamura, Kumamoto University; Tomonari Suzuki and Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Atsushi Natsume, Nagoya University, Nagoya, Japan; Shunsuke Terasaka, Hokkaido University, Hokkaido Prefecture, Japan; and Yi Qiao, and G_bor Marth, Boston College.


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Texas Children’s Hospital, a not-for-profit health care organization, is committed to creating a healthier future for children and women throughout the global community by leading in patient care, education and research. Consistently ranked as the best children’s hospital in Texas, and among the top in the nation, Texas Children’s has garnered widespread recognition for its expertise and breakthroughs in pediatric and women’s health. The hospital includes the Jan and Dan Duncan Neurological Research Institute; the Feigin Center for pediatric research; Texas Children’s Pavilion for Women, a comprehensive obstetrics/gynecology facility focusing on high-risk births; Texas Children’s Hospital West Campus, a community hospital in suburban West Houston; and Texas Children’s Hospital The Woodlands, a second community hospital planned to open in 2017. The organization also created the nation’s first HMO for children, has the largest pediatric primary care network in the country and a global health program that’s channeling care to children and women all over the world. Texas Children’s Hospital is affiliated with Baylor College of Medicine. For more information, go to Get the latest news by visiting the online newsroom and Twitter at