Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features

Extension of prostate cancer beyond the primary site into the surrounding organs by local invasion or nodal metastasis is associated with poor prognosis. The emergence and evolution of cancer clones at this early stage of expansion and spread has not been studied in detail. We performed whole genome...

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Vydané v:bioRxiv
Hlavní autori: Srinivasa Rao Rao, Verrill, Clare, Cerundolo, Lucia, Nasullah Khalid Alham, Kaya, Zeynep, O'hanlon, Miriam, Hayes, Alicia, Lambert, Adam, James, Martha, Tullis, Iain D C, Niederer, Jane, Lovell, Shelagh, Altan Omer, Lopez, Francisco, Leslie, Tom, Buffa, Francesca M, Bryant, Richard John, Lamb, Alastair D, Vojnovic, Boris, Wedge, David C, Mills, Ian G, Woodcock, Dan J, Tomlinson, Ian Pm, Hamdy, Freddie C
Médium: Paper
Jazyk:English
Vydavateľské údaje: Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.02.2023
Cold Spring Harbor Laboratory
Vydanie:1.2
Predmet:
Adenocarcinoma
Cancer Biology
Copy number
Evolution
Genetic transformation
Genomes
Lymph nodes
Lymphatic system
Metastases
Metastasis
Morphology
Prostate cancer
Prostatectomy
Seminal vesicle
Tumors
Vesicles
Whole genome sequencing
ISSN:2692-8205, 2692-8205
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Popis
Shrnutí:Extension of prostate cancer beyond the primary site into the surrounding organs by local invasion or nodal metastasis is associated with poor prognosis. The emergence and evolution of cancer clones at this early stage of expansion and spread has not been studied in detail. We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes. Based on these data, we delineated the route of tumour progression and metastasis following the transformation of adenocarcinoma to amphicrine morphology, the molecular events leading to whole genome duplication associated with a single clonal expansion and identified putative driver events associated with local invasion and lymph node metastasis. We also correlated genomic changes associated with differences in morphology and identified putative driver events associated with spread to seminal vesicle invasion and lymph node metastasis. Taken together, these findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes associated with morphological transformation. Our results demonstrate the value of integrating multi-region sequencing with histopathological data to study tumour evolution and identify mechanisms of prostate cancer spread.Competing Interest StatementThe authors have declared no competing interest.
Bibliografia:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ISSN:2692-8205
2692-8205
DOI:10.1101/2023.02.27.530113