The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy
Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-06-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13204 |
| _version_ | 1818252799047106560 |
|---|---|
| author | Johannes C. van derMijn Kenneth W. Eng Pooja Chandra Evan Fernandez Sinan Ramazanoglu Alexandros Sigaras Clara Oromendia Lorraine J. Gudas Scott T. Tagawa David M. Nanus Bishoy F. Faltas Himisha Beltran Cora N. Sternberg Olivier Elemento Andrea Sboner Juan Miguel Mosquera Ana M. Molina |
| author_facet | Johannes C. van derMijn Kenneth W. Eng Pooja Chandra Evan Fernandez Sinan Ramazanoglu Alexandros Sigaras Clara Oromendia Lorraine J. Gudas Scott T. Tagawa David M. Nanus Bishoy F. Faltas Himisha Beltran Cora N. Sternberg Olivier Elemento Andrea Sboner Juan Miguel Mosquera Ana M. Molina |
| author_sort | Johannes C. van derMijn |
| collection | DOAJ |
| description | Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy‐naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC. |
| first_indexed | 2024-12-12T16:29:55Z |
| format | Article |
| id | doaj.art-c682ec50c37c498fac15bed303bb33ff |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-12T16:29:55Z |
| publishDate | 2022-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-c682ec50c37c498fac15bed303bb33ff2022-12-22T00:18:48ZengWileyMolecular Oncology1574-78911878-02612022-06-0116122384239510.1002/1878-0261.13204The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapyJohannes C. van derMijn0Kenneth W. Eng1Pooja Chandra2Evan Fernandez3Sinan Ramazanoglu4Alexandros Sigaras5Clara Oromendia6Lorraine J. Gudas7Scott T. Tagawa8David M. Nanus9Bishoy F. Faltas10Himisha Beltran11Cora N. Sternberg12Olivier Elemento13Andrea Sboner14Juan Miguel Mosquera15Ana M. Molina16Department of Pharmacology Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USADepartment of Pharmacology Weill Cornell Medicine New York NY USADepartment of Pharmacology Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAEnglander Institute for Precision Medicine Weill Cornell Medicine New York NY USAPrimary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy‐naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC.https://doi.org/10.1002/1878-0261.13204cancergenomicsimmunotherapykidneymetastasisVEGF |
| spellingShingle | Johannes C. van derMijn Kenneth W. Eng Pooja Chandra Evan Fernandez Sinan Ramazanoglu Alexandros Sigaras Clara Oromendia Lorraine J. Gudas Scott T. Tagawa David M. Nanus Bishoy F. Faltas Himisha Beltran Cora N. Sternberg Olivier Elemento Andrea Sboner Juan Miguel Mosquera Ana M. Molina The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy Molecular Oncology cancer genomics immunotherapy kidney metastasis VEGF |
| title | The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy |
| title_full | The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy |
| title_fullStr | The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy |
| title_full_unstemmed | The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy |
| title_short | The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy |
| title_sort | genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy |
| topic | cancer genomics immunotherapy kidney metastasis VEGF |
| url | https://doi.org/10.1002/1878-0261.13204 |
| work_keys_str_mv | AT johannescvandermijn thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT kennethweng thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT poojachandra thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT evanfernandez thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT sinanramazanoglu thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT alexandrossigaras thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT claraoromendia thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT lorrainejgudas thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT scottttagawa thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT davidmnanus thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT bishoyffaltas thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT himishabeltran thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT coransternberg thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT olivierelemento thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT andreasboner thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT juanmiguelmosquera thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT anammolina thegenomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT johannescvandermijn genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT kennethweng genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT poojachandra genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT evanfernandez genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT sinanramazanoglu genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT alexandrossigaras genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT claraoromendia genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT lorrainejgudas genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT scottttagawa genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT davidmnanus genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT bishoyffaltas genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT himishabeltran genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT coransternberg genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT olivierelemento genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT andreasboner genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT juanmiguelmosquera genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy AT anammolina genomiclandscapeofmetastaticclearcellrenalcellcarcinomaaftersystemictherapy |