Sequencing of cancer cell subpopulations identifies micrometastases in a bladder cancer patient

Pathologic staging of bladder cancer patients remains a challenge. Standard-of-care histology exhibits limited sensitivity in detection of micrometastases, which can increase risk of cancer progression and delay potential adjuvant therapies. Here, we sought to develop a proof of concept novel molecu...

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Bibliographic Details
Published in:Oncotarget 2017-07, Vol.8 (28), p.45619-45625
Main Authors: Prado, Kris, Zhang, Kelvin X, Pellegrini, Matteo, Chin, Arnold I
Format: Article
Language:English
Subjects:
Alleles
Biomarkers
Female
Gene Frequency
Genetic Variation
Humans
Lymph Nodes - pathology
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Micrometastasis
Research Paper
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
Whole Exome Sequencing
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Summary:Pathologic staging of bladder cancer patients remains a challenge. Standard-of-care histology exhibits limited sensitivity in detection of micrometastases, which can increase risk of cancer progression and delay potential adjuvant therapies. Here, we sought to develop a proof of concept novel molecular approach to improve detection of cancer micrometastasis. We combined fluorescence activated cell sorting and next-generation sequencing and performed whole-exome sequencing of total cancer cells and cancer cell subpopulations in multiple tumor specimens and regional lymph nodes in a single patient with muscle-invasive urothelial carcinoma of the bladder following radical cystectomy. Mean allele frequency analysis demonstrated a significant correlation between primary tumor cancer cells and cancer cells isolated from the lymph nodes, confirming lymph node disease despite negative pathologic staging. RNA-sequencing revealed intratumoral heterogeneity as well as enrichment for immune system and lipid metabolism gene sets in the micrometastatic cancer cell subpopulations. Our analysis illustrates how next-generation sequencing of cancer cell subpopulations may be utilized to enrich for cancer cell markers and enhance detection of bladder cancer micrometastases to improve pathologic staging and provide insight into cancer cell biology.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.17312