Cancer Biomarkers - Volume 27, issue 3

Authors: Ma, Hongyun | Song, Bin | Guo, Shiwei | Li, Gang | Jin, Gang

Article Type: Research Article

Abstract: OBJECTIVES: Pancreatic cancer is one of the most lethal malignancies worldwide. Pancreatic adenosquamous carcinoma (PASC) is a rare histological type of pancreatic carcinoma with a poor prognosis. The median survival time after diagnosis is less than one year. It is believed that the pathogenesis of PASC is different from pancreatic adenocarcinoma. In this study, we tried to reveal the intrinsic gene mutations associated with PASC through whole exome sequencing. METHODS: Both cancerous and paracancerous tissues were collected from 12 pathologically diagnosed PASC patients. Their clinical characteristics were collected, and patient survival information was obtained through follow-up. …The correlations between the mutations and clinical characteristics were analysed. RESULTS: Germline mutations were identified in MAP3K1 (9 cases), PDE4DIP (7), BCR (7), ALK (6), USP6 (5), AR (4), HLA-A (4), SPEN (4), KMT2D (3), NUTM2B (3), ZFHX3 (3), and MN1 (3), while somatic mutations were found in TP53 (5), KRAS (3), HRNR (3), and OBSCN (3). Peripheral tissue invasion was associated with somatic mutations in KRAS (P = 0.0339). Additionally, there were significant correlations between lymphatic metastasis and germline mutations in USP6 (P = 0.0228) and somatic mutations in OBSCN and HRNR (P = 0.0339). CONCLUSION: In conclusion, susceptibility genes including MAP3K1 , PDE4DIP, and BCR are frequently found to be mutated in the germlines of PASC patients. Somatic mutations in KRAS , OBSCN, and HRNR and germline mutations in USP6 are related to tumour invasion and metastasis, reinforcing the necessity of translating these potential biomarkers into clinical practice. Show more

Keywords: Pancreatic adenosquamous carcinoma, germline mutation, somatic mutation, whole exome sequencing

DOI: 10.3233/CBM-190236

Citation: Cancer Biomarkers, vol. 27, no. 3, pp. 389-397, 2020

Authors: Melloul, S. | Mosnier, J.-F. | Masliah-Planchon, J. | Lepage, C. | Le Malicot, K. | Gornet, J.-M. | Edeline, J. | Dansette, D. | Texereau, P. | Delattre, O. | Laurent Puig, P. | Taieb, J. | Emile, J.-F.

Article Type: Research Article

Abstract: SMARCB1 is a tumor suppressor gene, which is part of SWI/SNF complex involved in transcriptional regulation. Recently, loss of SMARCB1 expression has been reported in gastrointestinal carcinomas. Our purpose was to evaluate the incidence and prognostic value of SMARCB1 loss in colon carcinoma (CC). Patients with stage III CC (n = 1695), and a second cohort of 23 patients with poorly differentiated CC were analyzed. Immunohistochemistry for SMARCB1 was performed on tissue microarrays, and cases with loss of expression were controlled on whole sections. Loss of SMARCB1 was compared with the clinico-pathological …and molecular characteristics, and the prognostic value was evaluated. Loss of SMARCB1 was identified in 12 of 1695 (0.7%) patients with stage III CC. Whole section controls showed a complete loss in only one of these cases, corresponding to a medullary carcinoma. SMARCB1 loss was not associated with histological grade, tumor size nor survival. In the cohort of poorly differentiated CC, we detected 2/23 (8.7%) cases with loss of SMARCB1; one was rhabdoid while the other had medullary and mucinous histology. These 2 cases were deficient for MisMatched Repair (dMMR) and mutated for BRAF . SMARCB1 loss is rare in stage III CC, but appears more frequent in poorly differentiated CC. Show more

Keywords: SMARCB1, colon carcinoma, BRAF V600E, mismatch repair deficiency

DOI: 10.3233/CBM-190287

Citation: Cancer Biomarkers, vol. 27, no. 3, pp. 399-406, 2020

Authors: Hurley, Laura C. | Levin, Nancy K. | Chatterjee, Madhumita | Coles, Jasmine | Muszkat, Shlomo | Howarth, Zachary | Dyson, Gregory | Tainsky, Michael A.

Article Type: Research Article

Abstract: BACKGROUND: The majority of ovarian cancer cases are diagnosed at an advanced stage with poor prognosis. This study evaluates autoantibodies against tumor antigens to identify candidate biomarkers for early detection of ovarian cancer in women at increased risk. OBJECTIVE: To assess the immunoreactivity of paraneoplastic antigens and tumor associated antigens with high-grade serous ovarian cancer (HGSOC) samples. METHODS: Five paraneoplastic antigens along with three tumor-associated antigens were evaluated with HGSOC patient serum samples. Validation screening was performed with n = 164 serum samples consisting of: 50 late stage …HGSOC, 14 early stage HGSOC, 50 benign ovarian cyst, and 50 healthy control samples on ELISA and western blot. The four markers TRIM21, NY-ESO-1, TP53, and PAX8 were evaluated on a second validation serum set, n = 150. RESULTS: TRIM21 achieved the highest sensitivity in the first validation screening of 33% with 100% specificity. Combining TRIM21 with NY-ESO-1, TP53, and PAX8 provided 67% sensitivity with 94% specificity, and 56% sensitivity at 98% specificity. These four markers resulted in 46% sensitivity with 98% specificity in the second validation cohort; TRIM21 achieved the highest individual sensitivity of 36%. CONCLUSIONS: Autoantibodies to TRIM21, NY-ESO-1, and TP53 may complement CA125 in screening of women at genetic risk for ovarian cancer. Show more

Keywords: Autoantibody, biomarker, ovarian cancer, paraneoplastic antigen

DOI: 10.3233/CBM-190988

Citation: Cancer Biomarkers, vol. 27, no. 3, pp. 407-421, 2020