Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations

Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations
최준혁W. D. Foulkes[W. D. Foulkes]Leanne de Kock[Leanne de Kock]Nelly Sabbaghian[Nelly Sabbaghian]Fran?ois Plourde[Fran?ois Plourde]Archana Srivastava[Archana Srivastava]Evan Weber[Evan Weber]Doroth?e Bouron?Dal Soglio[Doroth?e Bouron?Dal Soglio]Nancy Hamel[Nancy Hamel]Sung?Hye Park[Sung?Hye Park]Cheri L. Deal ·[Cheri L. Deal ·]Megan M. Kelsey[Megan M. Kelsey]Megan K. Dishop[Megan K. Dishop]Adam Esbenshade[Adam Esbenshade]John F. Kuttesch[John F. Kuttesch]Thomas S. Jacques[Thomas S. Jacques]Arie Perry[Arie Perry]Heinz Leichter[Heinz Leichter]Philippe Maeder[Philippe Maeder]Marie?Anne Brundler[Marie?Anne Brundler]Justin Warner[Justin Warner]James Neal[James Neal]Margaret Zacharin[Margaret Zacharin]M?rta Korbonits[M?rta Korbonits]Trevor Cole[Trevor Cole]Heidi Traunecker[Heidi Traunecker]Thomas W. McLean[Thomas W. McLean]Fabio Rotondo[Fabio Rotondo]Pierre Lepage[Pierre Lepage]Steffen Albrecht[Steffen Albrecht]Eva Horvath[Eva Horvath]Kalman Kovacs[Kalman Kovacs]John R. Priest[John R. Priest]
Issue Date
ACTA NEUROPATHOLOGICA, v.128, no.1, pp.111 - 122
Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis.
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