TY - JOUR
T1 - Intratumoral heterogeneity and chemoresistance in nonseminomatous germ cell tumor of the testis
AU - Bilen, Mehmet Asim
AU - Hess, Kenneth R.
AU - Campbell, Matthew T.
AU - Wang, Jennifer
AU - Broaddus, Russell R.
AU - Karam, Jose A.
AU - Ward, John F.
AU - Wood, Christopher G.
AU - Choi, Seungtaek L.
AU - Rao, Priya
AU - Zhang, Miao
AU - Naing, Aung
AU - General, Rosale
AU - Cauley, Diana H.
AU - Lin, Sue Hwa
AU - Logothetis, Christopher J.
AU - Pisters, Louis L.
AU - Tu, Shi Ming
N1 - Funding Information:
We thank Sunita Patterson from MD Anderson's Department of Scientific Publications for editing this manuscript. We thank Sarah Taylor for help with collection of cases and Nancy Ainslie, Cherie Perez, and Linda Yancey for help with compliance and regulatory issues. This work was supported in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant CA016672 (used the Clinical Trials Support Resource) and by a grant from the Realan Foundation and Mr. Harendra Mankodi (SMT). The patient population studied is a subset of a population described in reference 3.
PY - 2016
Y1 - 2016
N2 - Background: Nonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes. Results: Our institution's records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST). Patients with EYST had the highest cancer-specific mortality rate (P = .001). They tended to undergo somatic transformation (P = .0007). Two of 5 patients with clinical stage I EYST who had developed recurrence during active surveillance died of their disease. Materials and Methods: In this retrospective study, we evaluated consecutive patients who had been diagnosed with the three most common histological phenotypes of NSGCT. Chemoresistance was defined as the presence of teratoma, viable germ cell tumor, or somatic transformation in the residual tumor or the development of progressive or relapsed disease after chemotherapy. In a separate prospective study, we performed next-generation sequencing on tumor samples from 39 patients to identify any actionable genetic mutations. Conclusions: Our data suggest that patients with EYST in their primary tumor may harbor a potentially refractory NSGCT phenotype and are at increased risk of dying from disease. Despite intratumoral heterogeneity, improved patient selection and personalized care of distinct tumor subtypes may optimize the clinical outcome of patients with NSGCT.
AB - Background: Nonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes. Results: Our institution's records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST). Patients with EYST had the highest cancer-specific mortality rate (P = .001). They tended to undergo somatic transformation (P = .0007). Two of 5 patients with clinical stage I EYST who had developed recurrence during active surveillance died of their disease. Materials and Methods: In this retrospective study, we evaluated consecutive patients who had been diagnosed with the three most common histological phenotypes of NSGCT. Chemoresistance was defined as the presence of teratoma, viable germ cell tumor, or somatic transformation in the residual tumor or the development of progressive or relapsed disease after chemotherapy. In a separate prospective study, we performed next-generation sequencing on tumor samples from 39 patients to identify any actionable genetic mutations. Conclusions: Our data suggest that patients with EYST in their primary tumor may harbor a potentially refractory NSGCT phenotype and are at increased risk of dying from disease. Despite intratumoral heterogeneity, improved patient selection and personalized care of distinct tumor subtypes may optimize the clinical outcome of patients with NSGCT.
KW - Chemoresistance
KW - Intratumoral heterogeneity
KW - Next-generation sequencing
KW - Nonseminomatous germ cell tumor
KW - Testicular cancer
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U2 - 10.18632/oncotarget.13380
DO - 10.18632/oncotarget.13380
M3 - Article
C2 - 27861143
AN - SCOPUS:85007492096
SN - 1949-2553
VL - 7
SP - 86280
EP - 86289
JO - Oncotarget
JF - Oncotarget
IS - 52
ER -