Thématique :
- Cancer colorectal (CCR)
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Docteur Roger FAROUX
Coup de coeur :
  2016 Sep;151(3):440-447.e1  
  doi: 10.1053/j.gastro.2016.06.004  
  Frequent PIK3CA Mutations in Colorectal and Endometrial Tumors With 2 or More Somatic Mutations in Mismatch Repair Genes  
  Cohen SA, Turner EH, Beightol MB, Jacobson A, Gooley TA, Salipante SJ, Haraldsdottir S, Smith C, Scroggins S, Tait JF, Grady WM, Lin EH, Cohn DE, Goodfellow PJ, Arnold MW, de la Chapelle A, Pearlman R, Hampel H, Pritchard CC  


Some colorectal and endometrial tumors with microsatellite instability not attributable to MLH1 hypermethylation or germline mutations contain 2 or more somatic mutations in genes encoding mismatch repair (MMR) proteins. We sought to define the molecular phenotype of this newly recognized tumor subtype.


From 2 prospective studies of the efficacy of screening for Lynch syndrome, we identified patients with colorectal and endometrial tumors who had 2 or more somatic (but not germline) mutations in genes encoding MMR proteins (double somatic). We determined the frequencies of tumor mutations in PIK3CA, BRAF, KRAS, NRAS, and PTEN by targeted next-generation sequencing and used logistic-regression models to compare them with those from patients with Lynch syndrome, MLH1-hypermethylated, or microsatellite-stable tumors. We validated our findings using independent data sets from The Cancer Genome Atlas.


Among colorectal cancer cases, we found that 14 of 21 (67%) patients with double somatic tumors also had PIK3CA mutations, compared with 4 of 18 (22%) tumors from patients with Lynch syndrome, 2 of 10 (20%) tumors with MLH1 hypermethylation, and 12 of 78 (15%) tumors with microsatellite stability (P < .0001 for patients with double somatic tumors vs other subgroups). Mutations in PIK3CA were detected in all 13 patients with double somatic endometrial cancers (P = .04 compared with other subgroups). We did not detect BRAF mutations in patients with double somatic colorectal tumors or Lynch syndrome. We found highly similar results in a validation cohort from The Cancer Genome Atlas (113 patients with colorectal tumors, 178 endometrial tumors); 100% of double somatic cases had a somatic mutation in PIK3CA (P < .0001 compared with other subgroups).


Most patients with colorectal or endometrial tumors with 2 or more somatic (but not germline) mutations in MMR proteins also have mutations in PIK3CA; mutations in PIK3CA are detected at substantially higher frequencies in these double somatic tumors than in other microsatellite-instability subgroups. PIK3CA mutation status might be used to identify a specific group of colorectal tumors, and to select treatment or determine prognosis.

Question posée
Caractérisation de tumeurs doubles colorectales et endométriales avec instabilité microsatellitaire sans mutations germinales appelées « lynch-like ».
Question posée
Mutations PIK3CA significativement plus fréquente dans ce groupe de tumeurs doubles que dans les autres sous-groupes d’instabilité micro satellitaires ( Lynch, hyerméthylation MLH1).

Individualisation chez des  patientes ayant un « lynch-like syndrome » (double tumeur colon endomètre sans mutation germinale mais double mutation somatique) de mutations PIK3CA dans  67 % des cas.

La prise en charge de ces patientes soit comme des cancers sporadiques  soit de façon plus intensive reste  à déterminer.