MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer

Abstract Background Family history is one of the risk factors for pancreatic cancer. It is suggested that patients with pancreatic cancer who have a familial history harbor germline pathogenic variants of BRCA1 and/or BRCA2 (BRCA1/2), PALB2, or ATM. Recently, some germline variants of familial pancreatic cancers (FPCs), including PALB2, have been detected. Several countries, including Japan, perform screening workups and genetic analysis for pancreatic cancers. We have been carrying out active surveillance for FPC through epidemiological surveys, imaging analyses, and genetic analysis. Case presentation Here, we present the case of a female patient harboring pathogenic variants of PALB2 and NBN, with a family history of multiple pancreatic cancer in her younger brother, her aunt, and her father. Moreover, her father harbored a PALB2 pathogenic variant and her daughter harbored the same NBN pathogenic variant. Given the PALB2 and NBN variants, we designed surveillance strategies for the pancreas, breast, and ovary. Conclusions Further studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression.

Download Full-text

Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽

10.3390/cancers13071612 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1612

Author(s):

Julie Earl ◽

Emma Barreto ◽

María E. Castillo ◽

Raquel Fuentes ◽

Mercedes Rodríguez-Garrote ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Somatic Mutation ◽

Disease Status ◽

Clinical Analysis ◽

Cytotoxic Agents ◽

Disease Stage ◽

Ductal Adenocarcinoma ◽

Familial Pancreatic Cancer ◽

Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

Download Full-text

Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer

Cancer Discovery ◽

10.1158/2159-8290.cd-15-0402 ◽

2015 ◽

Vol 6 (2) ◽

pp. 166-175 ◽

Cited By ~ 145

Author(s):

Nicholas J. Roberts ◽

Alexis L. Norris ◽

Gloria M. Petersen ◽

Melissa L. Bondy ◽

Randall Brand ◽

...

Keyword(s):

Pancreatic Cancer ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genetic Heterogeneity ◽

Familial Pancreatic Cancer ◽

Whole Genome

Download Full-text

Risk independence for the identification of cystic lesions in Familial Pancreatic Cancer (FPC) kindreds

Pancreatology ◽

10.1016/j.pan.2017.05.215 ◽

2017 ◽

Vol 17 (3) ◽

pp. S68

Author(s):

Andrea Sheel ◽

Sara Harrison ◽

Ioannis Sarantitis ◽

James Nicholson ◽

Christopher Halloran ◽

...

Keyword(s):

Pancreatic Cancer ◽

Familial Pancreatic Cancer ◽

Cystic Lesions

Download Full-text

Differential mucin gene expression in human pancreatic and colon cancer cells

Biochemical Journal ◽

10.1042/bj2760599 ◽

1991 ◽

Vol 276 (3) ◽

pp. 599-605 ◽

Cited By ~ 42

Author(s):

S Yonezawa ◽

J C Byrd ◽

R Dahiya ◽

J J L Ho ◽

J R Gum ◽

...

Keyword(s):

Pancreatic Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Human Pancreatic Cancer ◽

Northern Blots ◽

Western Blots ◽

Pancreatic Cancer Cells

The purpose of this study was to determine the quantity and nature of the mucins synthesized and secreted by four different pancreatic cancer cell lines. Well- to moderately-differentiated SW1990 and CAPAN-2 human pancreatic cancer cells were found to produce more high-Mr glycoprotein (HMG) than less-differentiated MIA PaCa-2 and PANC-1 cells. Most of the labelled HMG was secreted within 24 h. The results of chemical and enzymic degradation, ion-exchange chromatography and density-gradient centrifugation indicated that the HMG in SW1990 and CAPAN-2 cells has the properties expected for mucins, whereas much of the HMG in MIA PaCa-2 and PANC-1 cells may not be mucin, but proteoglycan. These results are consistent with immunoblots and Northern blots showing the presence of apomucin and apomucin mRNA in SW1990 and CAPAN-2 cells, but not in MIA PaCa-2 and PANC-1 cells. The Western blots and Northern blots also show that SW1990 and CAPAN-2 cells, like breast cancer cells, have the mammary-type apomucin and mRNA coded by the MUC1 gene, but lack the intestinal type apomucin and mRNA coded by the MUC2 gene. In contrast, the colon cancer cell lines tested in culture express apomucin and mRNA coded by MUC2 but not by MUC1.

Download Full-text