Chromothripsis and progression-free survival in metastatic colorectal cancer

Skuja, Elīna; Kalniete, Dagnija; Nakazawa-Miklaševiča, Miki; Daneberga, Zanda; Āboliņš, Arnis; Purkalne, Gunta; Miklaševičs, Edvīns

doi:10.3892/mco.2017.1123

Cited by 14 publications

(20 citation statements)

References 11 publications

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“…A relation between prognosis and chromothripsis has been reported in several studies on different malignancies. In high risk neuroblastoma, breast cancer and MDS, chromothripsis is correlated with a poor outcome while in metastatic colorectal cancer a better progression free‐survival has been described . Probably metastases with chromothripsis respond better to therapy while the metastatic rate is higher in cancers harboring chromothripsis.…”

Section: Discussionmentioning

confidence: 99%

“…This is a phenomenon in which many genomic rearrangements occurs in a single chromosome or chromosome arm. It has been described in congenital abnormalities, UM and a variety of other cancers such as bone cancer, lung cancer, myelodysplastic syndrome (MDS), colorectal cancer, breast cancer and neuroblastoma . Chromothripsis predicts a poor outcome in skin melanoma and occur in high risk neuroblastoma, breast cancer and MDS .…”

Section: Introductionmentioning

confidence: 99%

“…Chromothripsis predicts a poor outcome in skin melanoma and occur in high risk neuroblastoma, breast cancer and MDS . A positive correlation between chromothripsis and progression free survival was observed in metastatic colorectal cancer . The clinical consequence of this phenomenon in UM remains unclear .…”

Section: Introductionmentioning

confidence: 99%

“…It has been described in congenital abnormalities, UM and a variety of other cancers such as bone cancer, lung cancer, myelodysplastic syndrome (MDS), colorectal cancer, breast cancer and neuroblastoma. 14,[17][18][19][20][21] Chromothripsis predicts a poor outcome in skin melanoma and occur in high risk neuroblastoma, breast cancer and MDS. 18,[20][21][22] A positive correlation between chromothripsis and progression free survival was observed in metastatic colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

“…18,[20][21][22] A positive correlation between chromothripsis and progression free survival was observed in metastatic colorectal cancer. 19 The clinical consequence of this phenomenon in UM remains unclear. 14 In this case series we report on chromothripsis in 7/249 UM.…”

Section: Introductionmentioning

confidence: 99%

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Chromosomal rearrangements in uveal melanoma: Chromothripsis

Poppelen

Yavuzyigitoglu

Smit

et al. 2018

Genes Chromosomes & Cancer

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Uveal melanoma (UM) is the most common primary intraocular malignancy in the Western world. Recurrent mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, EIF1AX, and SF3B1 are described as well as non‐random chromosomal aberrations. Chromothripsis is a rare event in which chromosomes are shattered and rearranged and has been reported in a variety of cancers including UM. SNP arrays of 249 UM from patients who underwent enucleation, biopsy or endoresection were reviewed for the presence of chromothripsis. Chromothripsis was defined as ten or more breakpoints per chromosome involved. Genetic analysis of GNAQ, GNA11, BAP1, SF3B1, and EIF1AX was conducted using Sanger and next‐generation sequencing. In addition, immunohistochemistry for BAP1 was performed. Chromothripsis was detected in 7 out of 249 tumors and the affected chromosomes were chromosomes 3, 5, 6, 8, 12, and 13. The mean total of fragments per chromosome was 39.8 (range 12‐116). In 1 UM, chromothripsis was present in 2 different chromosomes. GNAQ, GNA11 or CYSLTR2 mutations were present in 6 of these tumors and 5 tumors harbored a BAP1 mutation and/or lacked BAP1 protein expression by immunohistochemistry. Four of these tumors metastasized and for the fifth only short follow‐up data are available. One of these metastatic tumors harbored an SF3B1 mutation. No EIF1AX mutations were detected in any of the tumors. To conclude, chromothripsis is a rare event in UM, occurring in 2.8% of samples and without significant association with mutations in any of the common UM driver genes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chromosomal rearrangements in uveal melanoma: Chromothripsis

Poppelen

Yavuzyigitoglu

Smit

et al. 2018

Genes Chromosomes & Cancer

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Unravelling the tumour genome: The evolutionary and clinical impacts of structural variants in tumourigenesis

Hamdan

Ewing

2022

The Journal of Pathology

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Structural variants (SVs) represent a major source of aberration in tumour genomes. Given the diversity in the size and type of SVs present in tumours, the accurate detection and interpretation of SVs in tumours is challenging. New classes of complex structural events in tumours are discovered frequently, and the definitions of the genomic consequences of complex events are constantly being refined. Detailed analyses of short-read whole-genome sequencing (WGS) data from large tumour cohorts facilitate the interrogation of SVs at orders of magnitude greater scale and depth. However, the inherent technical limitations of short-read WGS prevent us from accurately detecting and investigating the impact of all the SVs present in tumours. The expanded use of long-read WGS will be critical for improving the accuracy of SV detection, and in fully resolving complex SV events, both of which are crucial for determining the impact of SVs on tumour progression and clinical outcome. Despite the present limitations, we demonstrate that SVs play an important role in tumourigenesis. In particular, SVs contribute significantly to late-stage tumour development and to intratumoural heterogeneity. The evolutionary trajectories of SVs represent a window into the clonal dynamics in tumours, a comprehensive understanding of which will be vital for influencing patient outcomes in the future. Recent findings have highlighted many clinical applications of SVs in cancer, from early detection to biomarkers for treatment response and prognosis. As the methods to detect and interpret SVs improve, elucidating the full breadth of the complex SV landscape and determining how these events modulate tumour evolution will improve our understanding of cancer biology and our ability to capitalise on the utility of SVs in the clinical management of cancer patients.

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Mutational game changer: Chromothripsis and its emerging relevance to cancer

Luijten

Lee

Crasta

2018

Mutation Research/Reviews in Mutation Research

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In recent years, the paradigm that genomic abnormalities in cancer cells arise through progressive accumulation of mutational events has been challenged by the discovery of single catastrophic events. One such phenomenon termed chromothripsis, involving massive chromosomal rearrangements arising all at once, has emerged as a major mutational game changer. The strong interest in this process stems from its widespread association with a range of cancer types and its potential as a mutational driver. In this review, we first describe chromothripsis detection and incidence in cancers. We then explore recently proposed underlying mechanistic origins, which explain the curious observations of the highly localised nature of the rearrangements on chromothriptic chromosomes. Detection of chromothriptic patterns following incorporation of single chromosomes into micronuclei or following telomere attrition have greatly contributed to our understanding of the reasons behind this chromosomal restriction. These underlying cellular events have been found to be participants in the tumourigenic process, strongly suggesting a potential role for chromothripsis in cancer development. Thus, we discuss potential implications of chromothripsis for cancer progression and therapy.

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Chromothripsis and progression-free survival in metastatic colorectal cancer

Cited by 14 publications

References 11 publications

Chromosomal rearrangements in uveal melanoma: Chromothripsis

Chromosomal rearrangements in uveal melanoma: Chromothripsis

Unravelling the tumour genome: The evolutionary and clinical impacts of structural variants in tumourigenesis

Mutational game changer: Chromothripsis and its emerging relevance to cancer

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