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Branching copy number evolution and parallel immune profiles across the regional tumor space of resected pancreatic cancer

Petersson, Alexandra (author)
Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Andersson, Natalie (author)
Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,Pathways of cancer cell evolution,Lund University Research Groups
Olsson Hau, Sofie (author)
Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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Eberhard, Jakob (author)
Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Karlsson, Jenny (author)
Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Chattopadhyay, Subhayan (author)
Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Valind, Anders (author)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
Elebro, Jacob (author)
Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Nodin, Björn (author)
Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Leandersson, Karin (author)
Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cancer Immunology, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Gisselsson Nord, David (author)
Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Jirström, Karin (author)
Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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 (creator_code:org_t)
2022
2022
English.
In: Molecular Cancer Research. - 1557-3125. ; 20:5, s. 749-761
Related links:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. The only option for curative treatment is resection of the tumor followed by standard adjuvant chemotherapy. Yet, early relapse due to chemoresistance is almost inevitable. Herein, we delineated the genetic intratumor heterogeneity in resected PDAC, with the aim to identify evolutionary patterns that may be associated with overall survival (OS) following treatment with curative intent. Potential relationships with the adjacent immune microenvironment were also examined. The genetic and immune landscapes of the regional tumor space were analyzed in nine patients with resected PDAC. Targeted deep sequencing and genome wide SNP array were followed by clonal deconvolution and phylogenetic analysis. A mathematical complexity score was developed to calculate the network extent of each phylogeny. Spatial variation in abundancy and tumor nest infiltration of immune cells was analyzed by double immunohistochemical staining. Copy number heterogeneity was denoted as the major contributing factor to the branching architectures of the produced phylogenetic trees. Increased tree complexity was significantly inversely associated with OS, and larger regional maximum aberrations (higher treetops) were associated with increased PD-L1 expression on tumor cells. Contrastingly, a FREM1 gene amplification, found in one patient, coincided with a particularly vigorous immune response. Findings from this limited case series suggest that complex evolutionary patterns may be associated with a shorter survival in surgically treated PDAC patients. Some hypothesis-generating associations with the surrounding immune microenvironment were also detected.Implications: Evolutionary copy number patterns may be associated with survival in patients with resected PDAC.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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