IllnessColorectal cancers, hereditary; differential diagnosis

NGS +

[Sanger]

Colorectal cancer (CRC) as common disease is the 3.rd most frequent cancer in men, the 2.nd most frequent in women. Hereditary CRC has two well-recognized forms: [A] Polyposis including familial adenomatous polyposis (FAP) and attenuated FAP caused by pathogenic variants in the APC gene, MUTYH-associated polyposis caused by pathogenic variants in the MUTYH gene. [B] Lynch syndrome - often referred to as hereditary non-polyposis CRC - caused by pathogenic germline variants in the DNA "mismatch repair" genes (MLH1, MSH2, MSH6, PMS2 genes) and EPCAM gene. Other CRC syndromes and their associated genes include oligopolyposis (POLE, POLD1 genes), NTHL1 gene, juvenile polyposis syndrome (BMPR1A, SMAD4 genes), Cowden (PTEN gene) and Peutz-Jeghers syndrome (STK11 gene). Many of these aforelisted syndromes are also associated with extra-colonic carcinomas as well as other manifestations. Serrated polyposis syndrome is characterized by hyperplastic polyps. In at least some cases, serrated polyposis syndrome also has familial components. Approximately one-quarter of CRC and/or adenoma cases appear to be familial, but only a portion of these are based on an identifiable hereditary syndrome. Most individuals with CRC diagnosed before age 50 who do not have a family history of cancer do not have pathogenic variants associated with a hereditary cancer syndrome. The DNA-diagnostic yield reaches >90%. Nevertheless a negative molecular genetic result does not exclude the clinical diagnosis with absolute certainty.

References: https://www.ncbi.nlm.nih.gov/books/NBK1211/

https://www.ncbi.nlm.nih.gov/books/NBK1345/

https://www.ncbi.nlm.nih.gov/books/NBK1469/

https://www.ncbi.nlm.nih.gov/books/NBK1266/

https://www.ncbi.nlm.nih.gov/books/NBK1488/

https://www.ncbi.nlm.nih.gov/books/NBK107219/

https://www.ncbi.nlm.nih.gov/books/NBK555473/

• Alias: Colon-Ca
• Alias: Darmkrebs
• Alias: Kolorektalkarzinom
• Alias: Rektum-Ca
• Allelic: Adenoma, periampullary, somatic (APC)
• Allelic: Adrenocortical carcinoma, pediatric (TP53)
• Allelic: Aplastic anemia (NBN)
• Allelic: Basal cell carcinoma 7 (TP53)
• Allelic: Birt-Hogg-Dube syndrome (FLCN)
• Allelic: Blepharocheilodontic syndrome 1 (CDH1)
• Allelic: Bone marrow failure syndrome 5 (TP53)
• Allelic: Brain tumor-polyposis syndrome 2 (APC)
• Allelic: Breast cancer, lobular (CDH1)
• Allelic: Breast cancer, somatic (TP53)
• Allelic: Breast cancer, susceptibility to (CHEK2)
• Allelic: Choroid plexus papilloma (TP53)
• Allelic: Desmoid disease, hereditary (APC)
• Allelic: Diarrhea 5, with tufting enteropathy, congenital (EPCAM)
• Allelic: Endometrial cancer, familial (MSH6)
• Allelic: Endometrial carcinoma, somatic (CDH1)
• Allelic: Endometrial carcinoma, somatic (MSH3)
• Allelic: Esophageal cancer, somatic (TGFBR2)
• Allelic: FILS syndrome (POLE)
• Allelic: Gastric cancer, hereditary diffuse, with/-out cleft lip and/or palate (CDH1)
• Allelic: Gastric cancer, somatic (APC)
• Allelic: Gastric cancer, somatic (MUTYH)
• Allelic: Glioma susceptibility 1 (TP53)
• Allelic: Hepatoblastoma, somatic (APC)
• Allelic: Hepatocellular carcinoma, somatic (TP53)
• Allelic: IMAGE-I syndrome (POLE)
• Allelic: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (SMAD4)
• Allelic: Leukemia, acute lymphoblastic (NBN)
• Allelic: Li-Fraumeni syndrome (CHEK2)
• Allelic: Li-Fraumeni syndrome (TP53)
• Allelic: Loeys-Dietz syndrome 2 (TGFBR2)
• Allelic: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (POLD1)
• Allelic: Melanoma, malignant, somatic (STK11)
• Allelic: Mismatch repair cancer syndrome (MLH1, MSH2, MSH6, PMS2)
• Allelic: Muir-Torre syndrome (MLH1, MSH2)
• Allelic: Myhre syndrome (SMAD4)
• Allelic: Nasopharyngeal carcinoma, somatic (TP53)
• Allelic: Nijmegen breakage syndrome (NBN)
• Allelic: Oligodontia-colorectal cancer syndrome (AXIN2)
• Allelic: Osteosarcoma (TP53)
• Allelic: Osteosarcoma, somatic (CHEK2)
• Allelic: Ovarian cancer, somatic (CDH1)
• Allelic: Pancreatic cancer, somatic (SMAD4)
• Allelic: Pancreatic cancer, somatic (STK11)
• Allelic: Pancreatic cancer, somatic (TP53)
• Allelic: Pneumothorax, primary spontaneous (FLCN)
• Allelic: Prostate cancer, familial, susceptibility to (CHEK2)
• Allelic: Prostate cancer, susceptibility to (CDH1)
• Allelic: Renal carcinoma, chromophobe, somatic (FLCN)
• Allelic: Testicular tumor, somatic (STK11)
• Adenomas, multiple colorectal (MUTYH)
• Adenomatous polyposis coli (APC)
• Breast and colorectal cancer, susceptibility to (CHEK2)
• Colorectal cancer (TP53)
• Colorectal cancer, hereditary nonpolyposis, type 1 (MSH2)
• Colorectal cancer, hereditary nonpolyposis, type 2 (MLH1)
• Colorectal cancer, hereditary nonpolyposis, type 4 (PMS2)
• Colorectal cancer, hereditary nonpolyposis, type 5 (MSH6)
• Colorectal cancer, hereditary nonpolyposis, type 6 (TGFBR2)
• Colorectal cancer, hereditary nonpolyposis, type 7 (MLH3)
• Colorectal cancer, hereditary nonpolyposis, type 8 (EPCAM)
• Colorectal cancer, somatic (APC)
• Colorectal cancer, somatic (AXIN2)
• Colorectal cancer, somatic (FLCN)
• Colorectal cancer, susceptibility to, 1 (GALNT12)
• Colorectal cancer, susceptibility to, 10 (POLD1)
• Colorectal cancer, susceptibility to, 12 (POLE)
• Colorectal cancer, susceptibility to, 3 (SMAD7)
• Cowden syndrome 1 (PTEN)
• Diamond Blackfan anaemia (RPS20)
• Familial adenomatous polyposis 1 (APC)
• Familial adenomatous polyposis 2 (MUTYH)
• Familial adenomatous polyposis 3 (NTHL1)
• Familial adenomatous polyposis 4 (MSH3)
• Gardner syndrome (APC)
• Juvenile polyposis syndrome, infantile form (BMPR1A)
• Lhermitte-Duclos syndrome (PTEN)
• Peutz-Jeghers syndrome (STK11)
• Polyposis syndrome, hereditary mixed, 2 (BMPR1A)
• Polyposis, juvenile intestinal (BMPR1A)
• Polyposis, juvenile intestinal (SMAD4)