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CANCER:

Ampulla of Vater Carcinoma

2d
The prognostic value of CAII and CAIX downregulation should be further investigated. Both isozymes may serve as biomarkers of epithelial dysplasia in the duodenum. (J Histochem Cytochem XX: XXX-XXX, XXXX).
Journal
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CA9 (Carbonic anhydrase 9)
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CA9 expression
6d
Majority of FAP patients with AAs did not experience CSP or require resection over 8 years of surveillance. Ampullary cancer was rare. Male gender, abnormal appearance of the papilla at AA detection, cholecystectomy and history of extracolonic malignancy are associated with CSP. Our findings favor endoscopic surveillance of AAs over expedited resection for most patients with FAP.
Journal
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APC (APC Regulator Of WNT Signaling Pathway)
10d
Beginning in 2018, consecutive patients presenting to our cancer center with nonmetastatic AC, DC or DCC were treated with upfront 5-FU and oxaliplatin based chemotherapy with concurrent 45Gy radiation ther- apy followed by surgical resection if possible... Neoadjuvant chemoradiation for these peri- ampullary cancers results in pathologic downstaging without an increased risk for treatment related morbidity or mortality. Long-term overall and relapse free survival outcomes following NT is necessary. Further assessment of germline and somatic alterations in these cancers is indi- cated.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset)
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BRCA1 mutation • KIT mutation • PMS2 mutation • BRCA mutation
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5-fluorouracil • oxaliplatin
15d
Alternative regimens include gemcitabine in combination with capecitabine...Pembrolizumab is approved for MSI-H tumors and tumors with high tumor mutational burden regardless of the primary site. Larotrectinib is approved for tumors with NTRK fusions. At a time when numerous therapeutic agents are in development, for example, those targeting specific K-RAS alterations or NRG fusions, identifying molecular aberrations can significantly impact patient outcomes as well as provide further insights into the biology of disease. In addition, based on recent data suggesting a significant prevalence of germline alterations in patients with ampullary tumors, referral to genetics counselors and germline testing is warranted in a significant proportion of patients with AC.
Review • Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK (Neurotrophic receptor tyrosine kinase)
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TMB-H • MSI-H/dMMR • NTRK fusion
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Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • gemcitabine • 5-fluorouracil • capecitabine • leucovorin calcium
22d
Clinically relevant tumors with complete or almost complete absence of MUC5AC staining included small cell carcinoma of the lung (0% of 17), clear cell renal cell carcinoma (0% of 507), papillary thyroid carcinoma (0% of 359), breast cancer (2% of 1097), prostate cancer (2% of 228), soft tissue tumors (0.1% of 968), and hematological neoplasias (0% of 111). The highly standardized analysis of a broad range of cancers identified a ranking order of tumors according to their relative prevalence of MUC5AC expression.
Journal
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MUC5AC (Mucin 5AC)
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MUC5AC expression
1m
The discrepant APC mutation frequency between adenomas and adenocarcinomas suggests that APC-mutated adenomas, which constitute the large majority of non-ampullary duodenal adenomas, are less prone to malignant transformation. Non-ampullary duodenal adenocarcinomas frequently exhibit MMR deficiency and should be subject to MMR testing to determine appropriate clinical management, including the identification of patients with Lynch syndrome.
Journal
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APC (APC Regulator Of WNT Signaling Pathway) • GNAS (GNAS Complex Locus) • MUC5AC (Mucin 5AC)
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APC mutation • MUC5AC expression
1m
In this long-term study of individuals with a CDKN2A mutation at high-risk for PDAC, we provide evidence that surveillance leads to detection of stage I, resectable PDAC with improved prognosis.
Clinical • Late-breaking abstract
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CDKN2A (Cyclin-dependent kinase inhibitor 2A)
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CDKN2A mutation
2ms
WNT signaling pathway was the major altered pathway in intestinal subtype. These mutated genes and pathways may be targeted with currently available drugs and may be explored for future development of targetable agents to improve the disease course in patients of AC.
Clinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMAD4 (SMAD family member 4)
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TP53 mutation • KRAS mutation • PIK3CA mutation
2ms
AC can be sporadic or be part of hereditary syndromes, in these cases, AC is associated with colorectal cancer. Association with BC is not well-illustrated. Some authors suggest that the BRCA2 gene muta- tion is a common risk factor of these tumours.
BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • GATA3 (GATA binding protein 3)
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BRCA2 mutation
2ms
Primary GI leiomyosarcomas are very rare. Most important entity on differential diagnosis is Gastrointestinal Stromal Tumour (GIST). In addition to this pathologist must always keep in mind leiomyosarcoma on the differential diagnosis of GIST’s.
KIT (KIT proto-oncogene, receptor tyrosine kinase)
2ms
SM-Ca lesions were all located on the oral-Vater and were highly associated with the gastric mucin phenotype, which were different from the features of most M-Ca.
Clinical • Journal
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MUC5AC (Mucin 5AC)
2ms
The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.
Clinical • Journal • Tumor Mutational Burden
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KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MDM2 (E3 ubiquitin protein ligase)
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PIK3CA mutation • KRAS G12D • KRAS G12V • KRAS G12R • KRAS G12 • APC mutation
2ms
Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.
Journal
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CD8 (cluster of differentiation 8)
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CD8 positive
2ms
These tumor entities need to be considered in cases of PLAP-positive metastasis. Low-level PLAP expression can be found in various other tumor entities and should generally not be viewed as a strong argument for germ cell neoplasia.
Journal
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ALPP (Alkaline Phosphatase, Placental)
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ALPP expression
3ms
Combination chemotherapy with gemcitabine and cisplatin is currently the standard of care for first-line chemotherapy in advanced cases...In the adjuvant setting, capecitabine monotherapy has become the standard of care in Western countries...Genetic testing is used to check for genetic alterations and molecular-targeted agents and immunotherapy are introduced based on tumor characteristics. In this article, we review the latest evidence of chemotherapy for biliary tract cancer.
Review • Journal • IO biomarker
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FGFR (Fibroblast Growth Factor Receptor)
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cisplatin • gemcitabine • 5-fluorouracil • capecitabine • leucovorin calcium
3ms
The majority of the reported cases of GISTs in the ampulla of Vater have been low risk with spindle-cell morphology, low mitotic figures, and minimal atypia; reactive for C-KIT and DOG-1; and nonreactive for SMA, desmin, and S100. In the majority of the cases, duodenectomy with or without Whipple's operation has been performed, and most of the cases showed good prognosis.
Review • Journal
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KIT (KIT proto-oncogene, receptor tyrosine kinase)
3ms
Preliminary data confirmed the safety of B+E and demonstrated evidence of anti-tumor activity in advanced cancer pts with non-V600E BRAF mts. Enrolment in the BEAVER trial is ongoing.
P2 data
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF D594G • BRAF D594N • BRAF G469S
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Braftovi (encorafenib) • Mektovi (binimetinib)
4ms
Mesothelin expression was unrelated to pathological tumor stage, grade, metastasis, and tumor infiltrating CD8+ lymphocytes. In conclusion, pancreatic cancer may be ideally suited for putative anti-mesothelin therapies, and mesothelin may represent a suitable biomarker for pancreatic cancer diagnosis, especially on small biopsies.
Journal
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CD8 (cluster of differentiation 8) • MSLN (Mesothelin)
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MSLN expression
4ms
We experienced a case in which pembrolizumab resulted in a complete response to MSI-H BTC. Since pembrolizumab for MSI-H BTC could prolong survival time, MSI examination should be performed proactively to increase treatment options.
Clinical • Journal • Microsatellite instability
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MSI (Microsatellite instability)
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MSI-H/dMMR
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Keytruda (pembrolizumab)
4ms
Thus, the cfDNA level could act as a surrogate marker of both disease extent and biological aggressiveness of ampullary cancer. Moreover, cfDNA plays a significant role in the prognosis of resectable ampullary cancer.
Journal
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CEACAM5 (CEA Cell Adhesion Molecule 5)
5ms
Conclusions MSI status and PDL-1 expression are characteristic of both intestinal and pancreatobiliary immunophenotypes of AC. To choose the treatment strategy and prescribe immunotherapy, it is necessary to search for predictive markers, one of which is to determine the expression of PD-L1 in ampullary carcinomas.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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PD-L1 expression
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VENTANA PD-L1 (SP263) Assay
5ms
Results In these 8 cases of resectable pancreatic/ampullary adenocarcinoma, 7 patients received mFOLFIRINOX adjuvant chemotherapy and 2 received additional rounds of gemcitabine/oxaliplatin and gemcitabine/paclitaxel. Conclusions Our findings suggest, presence of ctDNA after surgery in early-stage PDAC is associated with reduced recurrence-free survival. During monitoring, ctDNA was found to be a better prognostic marker compared to CA-19-9 and CEA and can be used to inform on disease status prior to imaging.
Clinical • Circulating tumor DNA
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CEACAM5 (CEA Cell Adhesion Molecule 5) • Cancer antigen 19-9
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Signatera™
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paclitaxel • gemcitabine • oxaliplatin
5ms
Compared to pancreatic cancer, B7-H3 is more frequently expressed in cancer cells of patients with the pancreato-biliary subtype of ampullary cancer. These data suggest that B7-H3 may represent an interesting potential target for immunotherapy in ampullary cancer rather than in pancreatic cancer.
Journal • IO biomarker
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CD276 (CD276 Molecule) • Cancer antigen 19-9
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CD276 expression
5ms
Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn's disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.
Review • Journal
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MUTYH (MutY homolog)
5ms
Following FOLFIRINOX (Fluorouracil/Leucovorin/Irinotecan/Oxaliplatin) administration and disease progression, nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) were administered every 3 weeks for 4 total cycles. Comprehensive genomic profiling is beneficial in periampullary adenocarcinomas as it can identify tumors with specific genetic characteristics, like MSI-high, dMMR or high TMB that respond well to immune checkpoint inhibitors. When these characteristics are present and the goal of treatment is to facilitate downstage and prolong progression free survival, nivolumab plus ipilimumab should be considered, but trials in periampullary adenocarcinomas are required to confirm usage.
Clinical • Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MSH2 (MutS Homolog 2)
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PD-L1 expression • TMB-H • MSI-H/dMMR • MSH2 mutation
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Opdivo (nivolumab) • Yervoy (ipilimumab) • oxaliplatin • irinotecan • leucovorin calcium
6ms
High expression was linked to advanced pathological tumor (pT) stage (p < 0.0001) and metastasis (p < 0.0001) in 1619 colorectal adenocarcinomas, but unrelated to parameters of malignancy in 1072 breast-, 386 ovarian-, 174 lung-, 757 kidney-, 171 endometrial-, 373 gastric-, and 925 bladder carcinomas. In summary, numerous important cancer types with high-level MSLN expression might benefit from future anti-MSLN therapies, but MSLN's prognostic relevance appears to be limited.
Journal
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MSLN (Mesothelin)
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MSLN expression • MSLN positive
6ms
Patients receive trastuzumab-pkrb 4mg/kg (after 6mg/kg load) D1, oxaliplatin 85mg/m2 D1, leucovorin 200mg/m2 D1, 5-FU 400mg/m2 bolus D1, and 5-FU 2400mg/m2 infusion D1-2 every 2 weeks until unacceptable toxicities or disease progression...As of February 2021, 16 patients have been enrolled . The pre-specified activity goal for the first stage of accrual was met; second stage accrual began in February 2021.
Clinical • P2 data
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive • HER-2 amplification
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Herceptin (trastuzumab) • cisplatin • gemcitabine • 5-fluorouracil • oxaliplatin • Herzuma (trastuzumab biosimilar) • leucovorin calcium
6ms
We found one classic EGFR activing mutation (L747_A750delinsP) and one MAP2K1 activating mutation (F53_Q58delinsL), which can be targeted by EGFR-TKIs and MEK inhibitor trametinib, respectively...We also found STK11/TSC2 inactivating mutations and a dominant-negative mutation of PTEN (R130Q) which could be targeted by mTOR inhibitor everolimus and AKT inhibitor capivasertib, respectively... The mutational landscape of our PDAC cohort provided compelling evidence that targetable driver mutations accounted for a significant portion of KRAS wide-type tumors . Our findings demonstrated that genomic profiling of PDAC patients can enable physicians to optimize their clinical management and enroll them into genomically matched clinical trials.
PARP Biomarker • BRCA Biomarker
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PALB2 (Partner and localizer of BRCA2) • TSC2 (TSC complex subunit 2) • NCOA4 (Nuclear Receptor Coactivator 4) • ELF3 (E74 Like ETS Transcription Factor 3)
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BRAF V600E • KRAS mutation • BRCA1 mutation • EGFR mutation • BRAF V600 • MET amplification • PTEN mutation • RET fusion • STK11 mutation • PALB2 mutation • BRAF fusion • TSC2 mutation • ERBB3 mutation • NCOA4-RET fusion • EGFR L747_A750delinsP
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Onco PanScan™
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Mekinist (trametinib) • everolimus • capivasertib (AZD5363)
6ms
This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • BAP1 (BRCA1 Associated Protein 1) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1)
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KRAS mutation • TMB-L • BAP1 mutation • SMAD4 mutation
6ms
Journal
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ANXA1 (Annexin A1) • ANXA10 (Annexin A10)
7ms
The BRAF N581I mutation is resistant to BRAF inhibitor vemurafenib but sensitive to MEK inhibitor trametinib. The PIK3CA N1044K mutation is oncogenic but its sensitivity to PIK3CA inhibitor alpelisib is unknown... Through comprehensive genomic characterization of Chinese AC patients, we identified multiple actionable mutations in multiple signaling pathways. Our findings indicated that molecular profiling can provide clinical benefits to a significant portion of AC patients.
Tumor Mutational Burden • MSi-H Biomarker • PARP Biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PALB2 (Partner and localizer of BRCA2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • SMAD4 (SMAD family member 4) • CHEK2 (Checkpoint kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ELF3 (E74 Like ETS Transcription Factor 3) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
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TP53 mutation • KRAS mutation • MSI-H/dMMR • HER-2 amplification • BRAF mutation • PIK3CA mutation • HER-2 mutation • FGFR2 mutation • FGFR2 amplification • PALB2 mutation • CHEK2 mutation • U2AF1 mutation • ERBB3 mutation • ERBB3 G284R • HER-2 R678Q
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Mekinist (trametinib) • Zelboraf (vemurafenib) • Piqray (alpelisib)
7ms
TempoSig enables rigorous identification of colibactin mutation signatures in clinically utilized MSK-IMPACT targeted exon datasets. SBS28+ CRCs are clinically distinct and associated with early onset, poor prognosis and DDR pathway alterations. In ongoing studies, we are investigating the therapeutic implications of these findings.
Clinical • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • ATR (Ataxia telangiectasia and Rad3-related protein)
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POLE mutation • TMB-L
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MSK-IMPACT
7ms
The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.
Journal • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMAD4 (SMAD family member 4)
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CTNNB1 mutation • SMAD4 mutation • APC mutation
7ms
Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.
Clinical • Journal
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CEACAM5 (CEA Cell Adhesion Molecule 5)
8ms
Patients with a high number of NADTs and/or high-grade dysplasia can be safely treated and followed by endoscopy. Spigelman classification seems outdated since not related to invasive cancer or need for surgery, in patients with regular follow-up and endoscopic resection.
Clinical
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APC (APC Regulator Of WNT Signaling Pathway)
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APC mutation
8ms
Systematic screening for cancer including CT-TAP in real-life practice revealed occult solid malignancy, mostly early-stage cancer, in a relevant proportion of patients presenting PMR-like symptoms. The high proportion of kidney cancer (40%) is worth highlighting, especially considering that it is not one of the most frequent cancers after 50 years of age.
Clinical • Journal
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CRP (C-reactive protein)
9ms
A specific cell population receiving Wnt-activating signal in periampullary PBGs functions as biliary epithelial stem/progenitor cells and also cellular origin of ampullary carcinoma.
Journal
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PTEN (Phosphatase and tensin homolog) • KRT19 (Keratin 19)
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PTEN deletion
over1year
Clinical • New P3 trial • Head-to-Head
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IL6 (Interleukin 6) • CRP (C-reactive protein)
2years
P, N=2000, Recruiting, George Zogopoulos
New trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
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ATM mutation • STK11 mutation • PALB2 mutation • CDKN2A mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation