Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Harnessing data science to advance radiation oncology

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Angiotensinogen promoter methylation predicts bevacizumab treatment response of patients with recurrent glioblastoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Using microarray-based subtyping methods for breast cancer in the era of high-throughput RNA sequencing

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Rare non-coding Desmoglein-2 variant contributes to Arrhythmogenic right ventricular cardiomyopathy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Fibrin thrombi in deceased donor kidneys: Prevalence and influence on graft function and graft survival in transplanted patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. High Expression of Legumain in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia is Associated with Central Nervous System Involvement

    Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

  5. Short-term spheroid culture of primary colorectal cancer cells as an in vitro model for personalizing cancer medicine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, while the other half was used for DNA and RNA purification. For two patients, lymph node metastases were analyzed. Somatic mutations were called from whole exome sequencing data. Each tumor contained mutations shared across all biopsies and spheroids, including major CRC drivers such as APC, KRAS, and TP53. At the same time, all tumors exhibited ITH on both mutation and copy number level. The concordance between biopsies and spheroids ranged between 40 and 70% for coding mutations. For three patients, the biopsy and spheroid from matching areas clustered together, meaning that the spheroid resembled the area of origin more than the other areas. However, all biopsies and spheroids contained private mutations. Therefore, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. Molecular subtypes were called from RNA sequencing data. When based on transcripts from both cancer and noncancerous cells, the subtypes were largely independent of sampling site. In contrast, subtyping based on cancer cell transcripts alone was dependent on sample site and genetic ITH. In conclusion, all examined CRC tumors showed genetic ITH. Spheroid cultures partly reflected this ITH, and having multiple cultures from distinct tumor sites improved the representation of the genetic tumor subclones. This should be taken into account when establishing patient-derived models for drug screening.

OriginalsprogEngelsk
TidsskriftMolecular Oncology
Vol/bind12
Udgave nummer1
Sider (fra-til)132-147
Antal sider16
ISSN1574-7891
DOI
StatusUdgivet - jan. 2018

ID: 55450232