Analysis of Colorectal Cancer driven by rare ALK-SLC12A2 Gene Fusion
The patient is a middle-aged female with ulcerative adenocarcinoma of the right colon, partly mucinous, invading the serous layer of the intestinal wall, parenteral lymph node metastasis, bilateral ovarian and uterine wall metastasis, involving the bilateral ureter.
Immunohistochemistry showed that there was no mismatch repair defect of MMR,pMMR.
The genetic test is MSS,TMB4.3Muts/Mb.TP53 C124Wfs*25 9.76% Sox GCN 4.59.
According to the results of the genetic testing company, the MSS, low TMB,TP53 frameshift inactivation mutation. Standard chemotherapy regimen can only be chosen after operation. After recurrence, we can only choose chemotherapy plus Bevacizumab。
So can we find useful information in a bunch of unknown genetic mutations? If you look carefully, there is indeed.
Among the many gene mutations, we lock on the fusion of SLC12A2-ALK gene. This is a rare new companion gene that is not recorded in the COSMIC database.
After querying the original data, it was found that the ALK fusion retained exon 20-29 of ALK, while the functional region of ALK gene and the bases encoding kinase active domain were downstream of exon 19, so it can be concluded that this ALK fusion is a pathogenic driving mutation.
ALK was first found in a subtype of anaplastic large cell lymphoma ((ALCL)), so it was named anaplastic lymphoma kinase (anaplastic lymphoma kinase,ALK). Subsequently, before the discovery of ALK gene rearrangement in non-small cell lung cancer, multiple types of ALK gene rearrangement were found in diffuse large B-cell lymphoma and inflammatory myofibroblastoma (IMT), which proved that ALK is a strong carcinogenic driver gene.
The incidence of ALK gene fusion in colorectal cancer ranges from 0.2% to 2.4%. Like ROS1/NTRK fusion, ALK gene fusion is a poor prognostic factor for colorectal cancer. Patients with ALK fusion have shorter OS. Compared with ALK wild type, OS was 15.6months vs33.7 months. (JNCI J Natl Cancer Inst (2017) 109 (12): ).
It has been reported that positive IHC ALK is a marker to predict whether Crizotinib is effective or not. NGS showed that when ALK was fused with IHC ALK (-), Crizotinib was not effective. Therefore, it is recommended to make an expression of IHC ALK protein.
The patient needs adjuvant treatment after operation. Whether it is possible to adopt the strategy of targeted maintenance after surgery in colorectal cancer has no data, and there is also a lack of large sample research. With reference to the maintenance strategy of lung cancer targeting drugs, colorectal cancer driven by ALK fusion should also be preferred to be maintained with alk inhibitors.
We also look forward to the corresponding clinical research.