Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers

Vécsey-Semjén, Beatrix; Becker, Karl‐Friedrich; Sinski, Alexandra; Blennow, Elizabeth; Vietor, Ilja; Zatloukal, Kurt; Beug, Hartmut; Wagner, Ernst; Huber, Lukas A.

doi:10.1038/sj.onc.1205577

Cited by 57 publications

(70 citation statements)

References 73 publications

(60 reference statements)

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“…This mutation was shown to harbour dramatic functional consequences in vitro [23]. Moreover, VecseySemjen and colleagues [24] found this same Ala634Val mutation in a colon carcinoma cell line and showed that this missense mutation results in the activation of a cryptic splice-site, leading to a premature stop codon. Both experiments support the pathogenic role of this germline missense mutation.…”

Section: Discussionmentioning

confidence: 92%

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

Oliveira

Ferreira

Nabais

et al. 2004

European Journal of Cancer

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Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations. In probands negative for CDH1 mutations, we screened genes involved in hereditary cancer syndromes in which gastric cancer may be one of the component tumours, namely p53 (Li-Fraumeni Syndrome) and hMLH1 and hMSH2 (HNPCC). We also screened in these patients for mutations in Caspase-10, a gene inactivated in sporadic gastric cancer, and SMAD4, a gene whose inactivation in mice is associated with signet-ring cell carcinoma of the stomach. One of the families fulfilling the HDGC criteria harboured a CDH1 germline mutation, and one of the families with incomplete criteria harboured a p53 germline mutation. No mutations were identified in hMLH1 and hMSH2, and only sequence variants were found in SMAD4 and Caspase-10. The present work reports for the first time CDH1 germline mutations in Portuguese gastric cancer families, and highlights the need for p53 mutation screening in families lacking CDH1 germline mutations, in a country with one of the highest incidences of gastric cancer in the world. No evidence was found for a role of germline mutations in SMAD4 and Caspase-10 in families lacking CDH1 mutations.

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Section: Discussionmentioning

confidence: 92%

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

Oliveira

Ferreira

Nabais

et al. 2004

European Journal of Cancer

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“…1), indicating that the genotype maintained strong control over the transcriptome. The only exception was the COGA5/COGA5L pair; these lines were derived respectively from the primary tumour and a lymph node metastasis of the same patient 14 .…”

Section: Resultsmentioning

confidence: 99%

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

et al. 2015

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The development of molecularly targeted anticancer agents relies on large panels of tumourspecific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available.

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“…GenBank accession number AC009082 version AC009082.7. 5 Vécsey-Semjén et al, 2002;Suriano et al, 2003a. 6 Guilford et al, 1998.…”

Section: Cdh1 Mutation Detectionmentioning

confidence: 99%

Identification of seven novel germline mutations in the human E-cadherin (CDH1) Gene

Humar

Weber

et al. 2007

Hum. Mutat.

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Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome caused by germline mutation of the gene encoding the tumour-suppressor E-cadherin (CDH1). We describe the search for CDH1 mutations in 36 new diffuse gastric cancer families. All 16 CDH1 exons, neighbouring intronic sequence and an essential promoter region were screened by DNA sequencing. We detected nine different mutations, seven of which were novel. Of the seven novel mutations, five were identified in families who met the IGCLC clinical criteria for HDGC. Two mutations resulted in a premature stop codon and truncation of the protein. Three mutations affected splice sites; two of the splice-site mutations were shown by RT-PCR to disturb normal CDH1 splicing, while the third splicesite mutation was present in two unrelated HDGC families. The remaining two mutations resulted in amino acid substitutions and impaired the ability of E-cadherin protein to form cellular aggregates and suppress invasion in vitro. Together with the occurrence of extragastric tumours such as lobular breast and colorectal cancer, these findings further extend the types of CDH1 mutations and the spectrum of tumours associated with HDGC.

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Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers

Cited by 57 publications

References 73 publications

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

Identification of seven novel germline mutations in the human E-cadherin (CDH1) Gene

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