Adult patients with metastatic or locally advanced solid malignancies (including but not limited to breast, cancer, lung adenocarcinoma or squamous cell carcinoma, colorectal cancer, ovarian cancer, renal clear cell cancer, skin cutaneous melanoma), presenting or having presented an exceptional and unexpected response to an antineoplastic targeted therapy.

The primary endpoint is the rate of patients with tumors harboring a low level of genomic alteration (mutation, amplification or deletion) in genes (i.e. mutation, amplification, deletion) identified as causally implicated in cancer. A low level of genomic alteration is defined by the presence of less than the 5th quantile of genomic alterations to be expected in the given tumor type. Conversely, a high level of genomic alteration is defined by the presence of more than the 5th quantile of genomic alterations to be expected in the given tumor type.

The list of genes for which alterations are identified as causally implicated in cancer is defined by the Cancer Gene Census. This is an ongoing effort to catalogue those genes for which mutations, amplifications or deletions have been causally implicated in cancer. It is constantly updated by the Wellcome Trust Sanger Institute (UK) and available at: http://cancer.sanger.ac.uk/census (n=571 genes in September 2015)

Inclusion Criteria:

1. Adult patient ( ≥18 years old at diagnosis).
2. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
3. Patient suffering from the following tumor type: breast cancer, lung adenocarcinoma or squamous cell carcinoma, colorectal cancer, ovarian cancer, renal clear cell cancer, skin cutaneous melanoma.
4. Metastatic or locally advanced disease.
5. Currently or previously treated with an anticancer targeted therapy in monotherapy. Targeted therapies combined with other agents are accepted only if 1/ the tumor was previously proven to be progressive under the same agents or 2/ the response or the stability has been maintained with the targeted therapy alone after the agent has been stopped.
6. Exceptional and unexpected tumor response to any marketed targeted therapy confirmed by the college of experts and defined as: complete response or partial response lasting more than six months, and not expected in more than 10% of the patients in this drug organ situation.
7. Availability and required quality of the tumor biopsy (FFPE or frozen sample) allowing for the whole exome sequencing analysis. Tumor biopsies obtained just before the initiation of the targeted therapy are preferred; otherwise any prior sample is possible.
8. Availability of normal tissue along with the tumor tissue, otherwise blood sample in order to extract constitutional DNA.

Exclusion Criteria:

1. Pediatric patient (<18 years old at diagnosis).
2. Hematological malignancy or solid tumors, which are not in the scope of tumor types described in the inclusion criteria.
3. Tumor sample not available or not reaching the required quality for whole exome sequencing analysis.
4. Absence of confirmation of the exceptional and unexpected pattern of response by the college of experts as defined above.