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Mutational Landscap...
Mutational Landscape in Resected Periampullary Adenocarcinoma: Relationship With Morphology and Clinical Outcome
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- Lundgren, Sebastian (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Institutionen för kliniska vetenskaper, Lund,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Department of Clinical Sciences, Lund,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Olsson Hau, Sofie (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Elebro, Jacob (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Heby, Margareta (author)
- Lund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Karnevi, Emelie (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Nodin, Björn (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Eberhard, Jakob (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Holm, Karolina (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Staaf, Johan (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups
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- Jönsson, Göran B (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups
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- Jirström, Karin (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Terapeutisk patologi,Institutionen för kliniska vetenskaper, Lund,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Personalized Pathology & Cancer Therapy,Lund University Research Groups,Therapeutic pathology,Department of Clinical Sciences, Lund
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(creator_code:org_t)
- 2019
- 2019
- English.
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In: JCO Precision Oncology. - 2473-4284. ; 3, s. 1-8
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Abstract
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- PURPOSE Periampullary adenocarcinomas encompass a heterogeneous group of tumors with dismal prognosisand limited treatment options. Emerging evidence shows that tumor morphology (ie, intestinal type [I-type] orpancreatobiliary type [PB-type]) is a more relevant prognostic factor than tumor origin. Knowledge is sparse,however, on whether key mutations differ according to morphology.MATERIALS AND METHODS Next-generation sequencing was applied to assess the mutational status of 70 genesin 102 tumors from a retrospective cohort of 175 patients with resected periampullary adenocarcinoma.Brahma-related gene 1 protein expression was examined by immunohistochemistry on tissue microarrays withprimary tumors from the original cohort.RESULTS APC mutations were significantly more common in I-type than in PB-type tumors (27.5% v 0%;P , .001), as were ERBB3 mutations (20.8% v 4.8%; P = .016), whereas CDKN2A mutations were morecommon in PB-type than in I-type tumors (19.4% v 2.5%; P = .013). KRAS mutation was an independentfactor of poor prognosis in I-type tumors (hazard ratio, 3.73; 95% CI, 1.10 to 12.67). In PB-type tumors,SMARCA4 mutation was an adverse prognostic factor in patients not receiving adjuvant chemotherapy,and there was a significant treatment interaction between expression of Brahma-related gene 1 protein, theprotein encoded by SMARCA4, and adjuvant chemotherapy (Pinteraction = .007).CONCLUSION To our knowledge, this is the first description of the mutational landscape in the full spectrum ofperiampullary adenocarcinoma that demonstrates that the distribution and prognostic and predictive significanceof commonly mutated genes differ by morphology. The results emphasize that morphology is an importantfactor to consider in the search for novel biomarkers and targeted personalized treatment of these patients. Inaddition, the findings support the concept that molecular profiling of these tumors could be of clinical benefit.
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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- art (subject category)
- ref (subject category)
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- By the author/editor
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Lundgren, Sebast ...
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Olsson Hau, Sofi ...
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Elebro, Jacob
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Heby, Margareta
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Karnevi, Emelie
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Nodin, Björn
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Eberhard, Jakob
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Holm, Karolina
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Staaf, Johan
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Jönsson, Göran B
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Jirström, Karin
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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JCO Precision On ...
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Lund University