Two-hit model for progression of medulloblastoma preneoplasia in Patched heterozygous mice

Oncogene
S PazzagliaA Saran

Abstract

Inactivation of one Ptc1 allele predisposes humans and mice to spontaneous medulloblastoma development, and irradiation of newborn Ptc1 heterozygous mice results in dramatic increase of medulloblastoma incidence. While a role for loss of wild-type (wt) Ptc1 (LOH) in radiation-induced medulloblastomas from Ptc1(neo67/+) mice is well established, the importance of this event in spontaneous medulloblastomas is still unclear. Here, we demonstrate that biallelic Ptc1 loss plays a crucial role in spontaneous medulloblastomas, as shown by high rate of wt Ptc1 loss in spontaneous tumors. In addition, remarkable differences in chromosomal events involving the Ptc1 locus in spontaneous and radiation-induced medulloblastomas suggest distinct mechanisms for Ptc1 loss. To assess when, during tumorigenesis, Ptc1 loss occurs, we characterized cerebellar abnormalities that precede tumor appearance in Ptc1(neo67/+) mice. We show that inactivation of only one copy of Ptc1 is sufficient to give rise to abnormal cerebellar proliferations with different degree of altered cell morphology, but lacking potential to progress to neoplasia. Furthermore, we identify biallelic Ptc1 loss as the event causally related to the transition from the preneoplastic...Continue Reading

References

Nov 11, 1992·Gynecologic Oncology·H H GallionJ R van Nagell
Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Oct 1, 1996·Journal of Intellectual Disability Research : JIDR·T MatsuishiY Fukushima
Jan 24, 1997·Cell·V E VelculescuK W Kinzler
Apr 24, 1997·Nature·K W Kinzler, B Vogelstein
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·A R ShoemakerW F Dove
Nov 24, 1999·Genes, Chromosomes & Cancer·R H ZurawelC Raffel
Apr 18, 2001·Current Opinion in Oncology·M ChintagumpalaS M Blaney
Nov 23, 2001·Journal of Neuro-oncology·R B Corcoran, M P Scott
Feb 2, 2002·Nature Reviews. Neuroscience·Ariel Ruiz i AltabaNadia Dahmane
Aug 31, 2002·Science·David M BermanPhilip A Beachy
Jul 3, 2003·Trends in Cell Biology·Stefan Linder, Martin Aepfelbacher
Jun 1, 2005·Cancer Letters·Simonetta Pazzaglia
Jul 8, 2005·Genes, Chromosomes & Cancer·Josena P KunjoonjuMaria J Worsham

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Citations

Jul 16, 2013·Clinical Oncology : a Journal of the Royal College of Radiologists·K T ButterworthK M Prise
Aug 20, 2008·Proceedings of the National Academy of Sciences of the United States of America·Mariateresa MancusoAnna Saran
Jul 29, 2008·Carcinogenesis·Mirella TanoriAnna Saran
Feb 12, 2010·Journal of Pediatric Hematology/oncology·Maria LuethPablo Hernáiz Driever
Mar 20, 2008·Expert Opinion on Therapeutic Targets·Pawel K Wlodarski, Jaroslaw Jozwiak
Oct 29, 2008·The Journal of Cell Biology·Jennifer M LeonardLarry M Karnitz
Feb 2, 2013·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Saori MatsuoMidori Yoshida
Sep 15, 2012·International Journal of Radiation Oncology, Biology, Physics·Mariateresa MancusoAnna Saran
Jul 17, 2015·Cell Cycle·Robert Ivkov, Fred Bunz
Aug 11, 2010·Trends in Molecular Medicine·Monique T BarakatMatthew P Scott
Feb 10, 2009·International Journal of Radiation Oncology, Biology, Physics·Simonetta PazzagliaAnna Saran
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Mariateresa MancusoDaniela Gallo
Mar 22, 2016·Cell Reports·Lukas Tamayo-OrregoFrédéric Charron
Sep 30, 2014·Developmental Cell·Frédéric MilleFrédéric Charron
Oct 15, 2014·Developmental Cell·Matthias Lauth, Rune Toftgard
Dec 20, 2007·Radiation Research·A SaranC Marino
Aug 12, 2018·Molecular Oncology·Yumei DiaoPeter G Zaphiropoulos
Jun 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Xing Fan, Charles G Eberhart
Oct 12, 2010·Journal of Neuro-oncology·Michael D ChanThomas E Ellis
Dec 10, 2016·Journal of Developmental Biology·Yesser H BelgacemLaura N Borodinsky
Mar 11, 2016·Molecular Cancer Therapeutics·Gessica FilocamoSimonetta Pazzaglia
Jul 29, 2019·Translational Oncology·Madiha NiyazSyed Mudassar
Nov 20, 2018·Experimental Neurology·Chiara Di PietroGlauco P Tocchini-Valentini
Aug 27, 2021·Current Oncology·Terence Teixeira DuarteRui Manuel Reis
Mar 11, 2010·Molecular Cancer·Mirella TanoriSimonetta Pazzaglia

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