Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma

Farris, Alton B.; Demicco, Elizabeth G.; Le, Long Phe; Finberg, Karin E.; Miller, Julie M.; Mandal, Rajni; Fukuoka, Junya; Cohen, Cynthia; Gaissert, Henning A.; Zukerberg, Lawrence; Lauwers, Gregory Y.; Iafrate, A. John; Mino‐Kenudson, Mari

doi:10.1097/pas.0b013e31820f18a2

Cited by 51 publications

(33 citation statements)

References 38 publications

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“…An important intrinsic factor that could possibly explain the difference in responsiveness is selective advantage due to intratumoral genetic heterogeneity, as was recently shown for renal cell carcinoma as a proof of principle. 27 This heterogeneity could be caused by microsatellite instability, 28 loss of heterozygosity, 29,30 and copy number variations. 31,32 Extrinsic factors include differences in oxygenation levels and cancer cell-stroma interactions.…”

Section: Discussionmentioning

confidence: 98%

Residual Esophageal Cancer after Neoadjuvant Chemoradiotherapy Frequently Involves the Mucosa and Submucosa

Shapiro

Kate²,

Hagen³

et al. 2013

Annals of Surgery

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After nCRT for esophageal cancer, both the mucosa and the submucosa show frequent residual malignant involvement. The surrounding stroma and the regional lymph nodes show the highest percentage of pCR and the overall regression pattern is most frequently a mixed pattern of both concentric regression and regression toward the lumen. This overall regression pattern lends support to careful testing of a wait-and-see approach in a subgroup of patients with esophageal cancer after nCRT.

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Section: Discussionmentioning

confidence: 98%

Residual Esophageal Cancer after Neoadjuvant Chemoradiotherapy Frequently Involves the Mucosa and Submucosa

Shapiro

Kate²,

Hagen³

et al. 2013

Annals of Surgery

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“…This pattern resembled that of CRC where a subset of tumors were hypermutated, largely attributable to microsatellite instability (MSI). Similarly, MSI-positive tumors have been reported to represent 7% of EAC 26 . These four cases with the highest mutation rates were found to be MSI-positive with the highest mutation frequency tumor having mutations in two mismatch repair genes MSH6 and MSH3 (Supplementary Table 15).…”

Section: Mutations Identified By Whole Exome Sequencingmentioning

confidence: 95%

Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

et al. 2013

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The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis.

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“…In addition to numerous histological classification schemes, several molecular GC classifications have been proposed in recent years, including from our own research group (25)(26)(27). In 2013, a classification system proposed by the Singapore-Duke group divided GC into proliferative, metabolic and mesenchymal subtypes, based on genetic and epigenetic expression of drug-responsive clusters (28).…”

Section: Gastric Cancermentioning

confidence: 99%

“…KRAS is a tumor suppressor gene which is located on chromosome 12p12 (www.genecards.org, accessed 8 th May 2015 ). It has six exons and alternative splicing of exon 4 produces KRAS4A and KRAS4B which contains 188 and 189 amino acids, respectively (27). KRAS encodes a small guanosine triphosphatase (GTPase) protein with a molecular mass of 21.6 kD (28).…”

Section: Krasmentioning

confidence: 99%

“…Final values were calculated by averaging the peak height of each probe and then averaging the results of replicates. Copy number thresholds were set based on previously published studies (25,27,28), with a DNA copy number >1.31 categorised as amplification. This analysis was performed separately for KCCH and LTHT cohorts.…”

Section: Kras Gene Copy Number and Data Analysesmentioning

confidence: 99%

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Prognostic and predictive biomarkers in oesophagogastric cancer

Hewitt¹

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Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma

Cited by 51 publications

References 38 publications

Residual Esophageal Cancer after Neoadjuvant Chemoradiotherapy Frequently Involves the Mucosa and Submucosa

Residual Esophageal Cancer after Neoadjuvant Chemoradiotherapy Frequently Involves the Mucosa and Submucosa

Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

Prognostic and predictive biomarkers in oesophagogastric cancer

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