Genomic characterisation of two cancers of unknown primary cases supports a kidney cancer origin.
Cancer of unknown primary (CUP) comprises of 3-5% of new cancer diagnoses in the USA. Diagnostic work up typically includes CT of the chest, abdomen and pelvis, and histopathological review of tissue specimens. These measures are neither sensitive nor specific in determining tissue of origin (ToO) of primary tumours and, therefore, are unable to guide therapy. We present two cases of CUP for which we utilised ultra-deep genomic sequencing to identify the candidate ToO and to propose treatment. Patient 1 presented with metastases involving the lung, lymph nodes and bone. Patient 2 presented with an acute pathological fracture of the T7 vertebral body and metastases involving the bone, lymph nodes and soft tissue. No primary renal mass was found. Sequencing revealed SETD2 and NF2 mutations, and heterozygous loss of the short arm of chromosome 3 (3p). Mutations in conjunction with clinicopathological features strongly support a diagnosis of renal cell carcinoma. Both patients initially responded to mTORC1 inhibition therapy.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Elizabeth Y
EY
Wei
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ying-Bei
YB
Chen
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
James J
JJ
Hsieh
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000188:drug therapy; D005260:Female; D023281:Genomics; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000235:genetics*; D017422:Sequence Analysis, DNA; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases