title: Chromothripsis and progression-free survival in metastatic colorectal cancer.
abstract: Metastatic dissemination of the primary tumor is the major cause of death in colorectal cancer (CRC) patients. Multiple chromosomal breaks and chromothripsis, a phenomenon involving multiple chromosomal fragmentations occurring in a single catastrophic event, are associated with cancer genesis, progression and developing of metastases. The aim of this study was to evaluate the effect of chromothripsis and total breakpoint count (breakpoint instability index) on progression-free survival (PFS). A total of 19 patients with metastatic CRC (mCRC) receiving FOLFOX first-line palliative chemotherapy between August, 2011 and October, 2012 were selected for this study. The results indicated that the highest breakpoint count was observed in chromosomes 1, 2 and 6. Chromothripsis was detected in 52.6% of the study patients. Furthermore, chromothripsis was associated with an increased median PFS (mPFS; 14 vs. 8 months, respectively; P=0.03), but an association with overall survival was not identified. The present study demonstrated that chromothripsis affected CRC patient survival, suggesting a role for this event as a prognostic and predictive marker in mCRC treatment.
authors.affiliation: Clinic of Oncology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia; Institute of Oncology, Riga Stradins University, LV-1007 Riga, Latvia.
authors.forename: Elina
authors.initials: E
authors.lastname: Skuja
authors.affiliation: Institute of Oncology, Riga Stradins University, LV-1007 Riga, Latvia.
authors.forename: Dagnija
authors.initials: D
authors.lastname: Kalniete
authors.affiliation: Institute of Oncology, Riga Stradins University, LV-1007 Riga, Latvia.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakazawa-Miklasevica
authors.affiliation: Institute of Oncology, Riga Stradins University, LV-1007 Riga, Latvia.
authors.forename: Zanda
authors.initials: Z
authors.lastname: Daneberga
authors.affiliation: Institute of Pathology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia.
authors.forename: Arnis
authors.initials: A
authors.lastname: Abolins
authors.affiliation: Clinic of Oncology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia; Institute of Oncology, Riga Stradins University, LV-1007 Riga, Latvia.
authors.forename: Gunta
authors.initials: G
authors.lastname: Purkalne
authors.affiliation: Institute of Oncology, Riga Stradins University, LV-1007 Riga, Latvia.
authors.forename: Edvins
authors.initials: E
authors.lastname: Miklasevics
keywords: breakpoint instability index; chromothripsis; metastatic colorectal cancer; progression-free survival