Entry |
|
Name |
Colorectal cancer |
Supergrp |
Mismatch repair deficiency [DS: H00876] |
Description |
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).
|
Category |
Cancer
|
Brite |
Human diseases [BR:br08402]
Cancers
Cancers of the digestive system
H00020 Colorectal cancer
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of digestive organs
Malignant neoplasms of intestine
Malignant neoplasms of large intestine
2B90 Malignant neoplasms of colon
H00020 Colorectal cancer
2B91 Malignant neoplasms of rectosigmoid junction
H00020 Colorectal cancer
2B92 Malignant neoplasms of rectum
H00020 Colorectal cancer
Tumor markers [br08442.html]
H00020
Cancer-accociated carbohydrates [br08441.html]
H00020
 |
Pathway |
hsa00512 | Mucin type O-glycan biosynthesis |
|
Network |
|
Element |
N00012 | Mutation-activated KRAS/NRAS to ERK signaling pathway |
N00032 | Mutation-activated KRAS/NRAS to PI3K signaling pathway |
N00041 | EGFR-overexpression to RAS-ERK signaling pathway |
N00042 | EGFR-overexpression to PI3K signaling pathway |
N00057 | Mutation-inactivated APC to Wnt signaling pathway |
N00058 | Mutation-activated CTNNB1 to Wnt signaling pathway |
N00064 | Mutation-inactivated TGFBR2 to TGF-beta signaling pathway |
N00065 | Mutation-inactivated SMAD2 to TGF-beta signaling pathway |
N00099 | Mutation-inactivated BAX to apoptotic pathway |
N00102 | Loss of DCC to DCC-apoptotic pathway |
N00104 | Mutation-activated KRAS to RalGDS signaling pathway |
N00115 | Mutation-inactivated TP53 to transcription |
N00230 | TGFA-overexpression to RAS-ERK signaling pathway |
N00232 | TGFA-overexpression to PI3K signaling pathway |
N00276 | EGF-overexpression to RAS-ERK signaling pathway |
N00278 | EREG-overexpression to RAS-ERK signaling pathway |
N00280 | AREG-overexpression to RAS-ERK signaling pathway |
N00281 | EGF-overexpression to PI3K signaling pathway |
N00283 | EREG-overexpression to PI3K signaling pathway |
N00285 | AREG-overexpression to PI3K signaling pathway |
|
Gene |
beta-Catenin (mutation) [HSA: 1499] [KO: K02105]
K-ras (mutation) [HSA: 3845] [KO: K07827]
APC (germline mutation (FAP), somatic mutation) [HSA: 10297] [KO: K02085]
DCC (deletion) [HSA: 1630] [KO: K06765]
TGF-betaRII (mutation) [HSA: 7048] [KO: K04388]
Smad2 (mutation) [HSA: 4087] [KO: K04500]
Smad4 (deletion) [HSA: 4089] [KO: K04501]
BAX (mutation) [HSA: 581] [KO: K02159]
p53 (deletion) [HSA: 7157] [KO: K04451]
MLH1 (germline mutation (HNPCC), LOH, promoter hypermethylation) [HSA: 4292] [KO: K08734]
MSH2 (germline mutation (HNPCC), LOH, somatic mutation) [HSA: 4436] [KO: K08735]
MSH3 (somatic frameshift mutation) [HSA: 4437] [KO: K08736]
MSH6 (germline mutation (HNPCC), LOH, somatic frameshift mutation) [HSA: 2956] [KO: K08737]
GALNT12 (germline mutation, somatic mutation) [HSA: 79695] [KO: K00710]
EGF (overexpression) [HSA: 1950] [KO: K04357]
TGFA (overexpression) [HSA: 7039] [KO: K08774]
EREG (overexpression) [HSA: 2069] [KO: K09784]
AREG (overexpression) [HSA: 374] [KO: K09782]
|
Carcinogen |
Mineral oils, untreated and mildly treated
X- and gamma-radiation
|
Drug |
Capecitabine [DR: D01223]
Floxuridine [DR: D04197]
Trifluridine and tipiracil hydrochloride [DR: D10526]
Oxaliplatin [DR: D01790]
Cetuximab [DR: D03455] (K-Ras wild type, EGFR-expressing)
Bevacizumab [DR: D06409]
Panitumumab [DR: D05350] (K-Ras wild type)
Nivolumab [DR: D10316] (microsatellite instability-high)
Pembrolizumab [DR: D10574] (microsatellite instability-high)
Ramucirumab [DR: D09371]
Regorafenib hydrate [DR: D10137]
Irinotecan hydrochloride [DR: D01061]
Aflibercept [DR: D09574]
Leucovorin calcium [DR: D01211]
Levoleucovorin calcium [DR: D04715]
Calcium levofolinate hydrate [DR: D11555]
Sodium levofolinate [DR: D11394]
|
Comment |
ICD-O: 8140/3, Tumor type: Adenocarcinoma
|
Other DBs |
|
Reference |
|
Authors |
Grady WM. |
Title |
Genomic instability and colon cancer. |
Journal |
|
Reference |
|
Authors |
Houlston RS. |
Title |
What we could do now: molecular pathology of colorectal cancer. |
Journal |
|
Reference |
|
Authors |
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP. |
Title |
Microsatellite instability in colorectal cancer. |
Journal |
|
Reference |
|
Authors |
Lynch HT, de la Chapelle A. |
Title |
Hereditary colorectal cancer. |
Journal |
|
Reference |
|
Authors |
Mehlen P, Fearon ER. |
Title |
Role of the dependence receptor DCC in colorectal cancer pathogenesis. |
Journal |
|
Reference |
|
Authors |
Tolbert PE. |
Title |
Oils and cancer. |
Journal |
Cancer Causes Control 8:386-405 (1997) |
Reference |
|
Authors |
Berrington de Gonzalez A, Darby S. |
Title |
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. |
Journal |
|
Reference |
(drug) |
Authors |
Papadakis MA and McPhee SJ |(ed) |
Title |
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition |
Journal |
McGraw Hill Education |
Reference |
|
Authors |
Guda K, Moinova H, He J, Jamison O, Ravi L, Natale L, Lutterbaugh J, Lawrence E, Lewis S, Willson JK, Lowe JB, Wiesner GL, Parmigiani G, Barnholtz-Sloan J, Dawson DW, Velculescu VE, Kinzler KW, Papadopoulos N, Vogelstein B, Willis J, Gerken TA, Markowitz SD |
Title |
Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. |
Journal |
|
Reference |
|
Authors |
Hayashi Y, Widjono YW, Ohta K, Hanioka K, Obayashi C, Itoh K, Imai Y, Itoh H |
Title |
Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues. |
Journal |
|
Reference |
|
Authors |
Spano JP, Fagard R, Soria JC, Rixe O, Khayat D, Milano G |
Title |
Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives. |
Journal |
|
Reference |
|
Authors |
Di Fiore F, Sesboue R, Michel P, Sabourin JC, Frebourg T |
Title |
Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer. |
Journal |
|
Reference |
|
Authors |
Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD, Fidler IJ |
Title |
Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. |
Journal |
Clin Cancer Res 1:19-31 (1995) |
LinkDB |
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