• Is consistent with OR has been diagnosed with one of the following:

‣ Colorectal cancer: stage IV

⁃ Non-small cell or small cell lung cancer: stage III/IV

⁃ Prostate cancer: metastatic prostate cancer

⁃ Gastric cancer, not otherwise specified (NOS): stage IV

⁃ Esophageal cancer, NOS: stage IV

⁃ Adenocarcinoma of gastroesophageal junction: stage IV

⁃ High grade serous ovarian cancer: stage III/IV

⁃ Invasive breast carcinoma: stage III/IV

⁃ Melanoma: stage III/IV

⁃ Acute myeloid leukemia

⁃ Multiple myeloma

• For the purposes of this study,

‣ Re-staging is allowed

⁃ Having more than one primary cancer is allowed, if the patient is being treated solely for one of the eligible cancers listed above

• Patient should fit in one of the following four clinical scenarios (a-d)

‣ Undergoing diagnostic workup for one of the diseases listed for which treatment will likely include a new regimen of standard of care therapy OR

⁃ Scheduled to begin treatment with a new regimen of standard of care therapy OR

⁃ Currently progressing on a regimen of standard of care therapy OR

⁃ Currently being treated with a regimen standard of care therapy, without evidence of progression

• Requirements for fresh tissue biospecimen collections at enrollment:

‣ For clinical scenarios a, b, and c above, freshly collected tumor tissue or bone marrow (BM) aspirate must be submitted at enrollment

• For clinical scenarios a and b, the fresh tissue collection must be prior to starting therapy

∙ For clinical scenario a, the biospecimen collection must be part of a standard of care medical procedure

∙ For clinical scenarios b or c, the biospecimen collection may be part of a standard of care medical procedure OR

∙ The biospecimen collection may be part of a study-specific procedure (research only biopsy), when the patient has a tumor amenable to image guided or direct vision biopsy and is willing and able to undergo a tumor biopsy for molecular profiling

‣ Note: For research-only biopsies, the biopsy must not be associated with a significant risk of severe or major complications or death; the procedure cannot be a mediastinal, laparoscopic, open or endoscopic biopsy; nor can the procedure be a brain biopsy; nor can the patient be under the age of majority as determined by each U.S. state

• Requirements for archival tissue:

‣ For clinical scenarios a and b above, archival tissue as outlined below must be submitted IF AVAILABLE

⁃ For clinical scenarios c and d above, archival tissue as outlined below is REQUIRED

⁃ Pre-existing archival material (formalin-fixed, paraffin-embedded \[FFPE\] block, BM aspirate, or unstained slides) that:

• Contains the cancer type for which the participant is enrolled, and

∙ Was collected no more than 5 years prior to initiation of therapy, and

∙ Contains at least a surface area of 5 mm\^2 and optimal surface area of 25 mm\^2 or 3-5 mL cryopreserved bone marrow aspirate to yield 200 million bone marrow mononuclear cells, and

∙ Contains at least 10% tumor content. 70% tumor content is optimal, and

∙ No more than 1 line of standard of care systemic therapy was administered from the date of archival material collection to the date of initiation of therapy

• Requirements for blood collection: ALL scenarios require fresh blood collection at enrollment

‣ Blood collection for clinical scenarios a, b, and c must take place within 1 week of fresh tumor specimen collection

⁃ Blood collection for clinical scenario d must take place within 4 weeks of enrollment, and while patient is on treatment

• Age 13 or older

• Any sex

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

• Ability to understand and willingness to sign an informed consent document. Consent may be provided by a Legally Authorized Representative (LAR) in accordance with 45 CFR 46.102(i)

• NCI PDMR INCLUSION CRITERIA: Patients with CRC with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) status

• NCI PDMR INCLUSION CRITERIA: Patients with CRC who are 40 years old or younger at time of collection irrespective of mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) status

• NCI PDMR INCLUSION CRITERIA: Patients with BRCA that are either

‣ Any race/ethnicity with hormone receptor positive (ER+PR+, ER+PR-, or ER-PR+)

⁃ African American with triple negative (ER-PR-HER2-)

• NCI PDMR INCLUSION CRITERIA: Patients with lung cancer (LCA), prostate cancer (PCA), gastroesophageal cancer (GEC), ovarian cancer (OV), acute myeloid leukemia (AML), multiple myeloma (MML)