Open AccessClonal evidence for the development of neuroblastoma with extensive copy‐neutral loss of heterozygosity arising in a mature teratoma
Author(s) -
Ono Rintaro,
Ueno Hiroo,
Yoshida Kenichi,
Takahashi Satoko,
Yoshihara Hiroki,
Nozaki Taiki,
Suzuki Koyu,
Nakazawa Atsuko,
Saiki Ryunosuke,
Seki Masafumi,
Takita Junko,
Ogawa Seishi,
Manabe Atsushi,
Hasegawa Daisuke
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14931
Subject(s) - loss of heterozygosity , neuroblastoma , germline , biology , teratoma , exome sequencing , cancer research , malignant transformation , immature teratoma , genetics , mutation , gene , pathology , allele , germ cell tumors , medicine , cell culture , chemotherapy
Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole‐exome sequencing identified extensive copy‐neutral loss of heterozygosity (LOH) in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma. In addition, several truncating germline heterozygous variants in tumor suppressor genes, including RBL2 and FBXW12 , became homozygous as a result of LOH. Collectively, we speculate that extensive LOH in teratoma cells may force heterozygous germline variants to become homozygous, which, in turn, may contribute to the development of neuroblastoma with the acquisition of additional chromosomal changes.